Neonatal FcR Expression in Bone Marrow-Derived Cells Functions to Protect Serum IgG from Catabolism¹

Effective humoral immunity requires a high concentration of Abs. Although IgA is the main Ab associated with the gut, IgG is the predominant isotype present in the blood and extravascular space. Ag-specific IgG titers correlate well with protection against infection, toxin neutralization, and vaccine efficacy. Consistent with this important role in immune protection, IgG has a long half-life in the circulation, longer than most serum molecules (1).

The long serum half-life of IgG and albumin is mediated by the β₂-microglobulin-dependent class I-like molecule neonatal FcR (FcRn)³ (2, 3, 4). The existence of FcRn was first demonstrated by the isolation of a heterodimeric receptor that mediates transfer of maternal IgG to the newborn across the small intestine of rodent (5, 6, 7, 8). Subsequently, the discovery of the low serum IgG levels present in β₂-microglobulin mice (deficient in the obligate L chain of FcRn) suggested that FcRn was also responsible for protecting serum IgG from catabolism (2, 9, 10, 11). Finally, proof that FcRn is indeed the homeostatic IgG receptor came with the observations of the short IgG serum half-life and low serum IgG levels present in recently generated FcRn H chain-deficient animals (3).

FcRn is thought to have three functional modes of interaction with IgG. First, FcRn has been shown to transcytose IgG across a polarized epithelial cell layer both in vitro and in vivo (12). This function of FcRn allows the absorption of maternal IgG by the newborn across the small intestine or the placenta. Second, FcRn can bind to internalized IgG in an acidic endosome and recycle it back to the cell surface (13). This function of FcRn protects internalized IgG from catabolism. Lastly, a recent report has suggested that FcRn may also function as a phagocytic receptor in neutrophils (14).

To protect serum IgG from catabolism, FcRn is predicted to function at sites that have a large contact area with the blood such as the vascular endothelium of the skin and skeletal muscle (15). In fact, FcRn has been shown to be highly expressed in a variety of different endothelial beds. A significant body of work has established that FcRn, expressed in endothelial cells, intercepts internalized IgG and returns it to the circulation thus protecting it from lysosomal degradation (13, 15, 16, 17, 18). Although expression of the homeostatic IgG receptor in the vascular endothelium makes logical sense, FcRn is also expressed at other sites in adult animals. Some of these sites, such as the liver (19, 20) and kidney (21, 22, 23), also have a large exposure to serum IgG. It is therefore conceivable that FcRn may contribute to the preservation of circulating IgG at these sites. Although the role of endothelial cell expression of FcRn in maintenance of serum IgG levels is well accepted, the role of FcRn in other cell types and at its extravascular sites of expression is less defined. Importantly, it is not known whether FcRn expressed at these other sites contributes significantly to serum IgG homeostasis.

Because a comprehensive survey of FcRn expression in mouse tissues has not yet been performed, we first generated a mouse FcRn-specific antiserum and used it to stain a variety of tissues in the mouse. To confirm expression in tissues, we used the recently generated FcRn-deficient mice as a specificity control (3). These studies confirmed that FcRn is highly expressed in the vascular endothelium. We also found significant expression of FcRn in bone marrow-derived cells. Unexpectedly, bone marrow chimeras showed that hemopoietically derived phagocytic cells contribute to significantly extend the half-life of serum IgG.

FcRn-deficient mice (backcrossed at least 13 generations onto the C57BL/6J background) have been described previously (3). B6.PL-Thy1^a/CyJ (Thy1.1 congenic mice) were purchased from The Jackson Laboratory. All mice were housed in specific pathogen-free facilities at Washington University (St. Louis, MO) or at The Jackson Laboratory and used according to standard animal use protocols with approval of the Institutional Animal Care and Use Committee.

Age- and sex-matched wild-type or FcRn-deficient mice (2–4 mo of age) were euthanized by CO₂ inhalation. Neonatal proximal small intestine was obtained from 10-day-old pups which were euthanized by decapitation. Organs (except those noted below) were extracted and embedded directly in Tissue Tek OCT compound (Sakura), flash-frozen in dry ice-cooled 2-methyl butane, and stored at −80°C until sectioning. Seven-micrometer frozen sections were cut at −20°C and applied to SuperFrost Plus slides (Fisher Scientific). For gut tissues, organs were flushed with PBS and then inflated with OCT compound to properly support the tissue for sectioning. Lung tissues were inflated via tracheal intubation with 1 ml of a 50–50 mixture of OCT compound in PBS and then processed as described above.

Armenian Hamster lung carcinoma AHL-1 cells were transiently transfected with a cytoplasmic tail-deleted construct of mouse FcRn using FuGENE6 reagent (Roche) according to the manufacturer’s instructions. We used a tail-deleted version of FcRn because full-length FcRn is normally expressed intracellularly in endosomes and we were concerned that this form of the Ag would not be efficiently presented. In contrast, the tail-deleted FcRn construct results in cell surface expression of mouse FcRn paired with hamster β₂-microglobulin. We verified the functionality of this hybrid FcRn molecule by its ability to bind IgG at pH 6 but not at pH 7.4 in a FACS-based assay as described previously (24). A total of 5–10 × 10⁶ transiently transfected cells were emulsified with an equal volume of CFA H37Ra (Difco) and Armenian Hamsters were immunized i.p. with 1 ml of emulsion. Boosts were performed similarly at 3-wk intervals except that transfected cells were emulsified in IFA (Sigma-Aldrich). Antisera were screened by flow cytometry on HEK293 cells stably transfected with GFP-tagged mouse or human FcRn expressed on the cell surface. Terminal bleed antiserum was collected by cardiac puncture. Hamster handling and immunization was performed by the Washington University School of Medicine Hybridoma Center.

For surface staining, cells were stained with a 1/1000 dilution of anti-FcRn antiserum in FACS buffer (PBS plus 2% FCS). For intracellular staining, cells were first fixed for 10 min with 1% paraformaldehyde in PBS, washed with PBS, and blocked/permeabilized with FACS buffer with 0.1% saponin. Intracellular staining was performed with a 1/1000 dilution of anti-FcRn antiserum. To detect FcRn, secondary anti-hamster-FITC, -PE, or -Cy5 reagents were used (Jackson ImmunoResearch Laboratories and BD Pharmingen). Before staining for APCs, cells were preincubated for 15 min with a 1/100 dilution of anti-CD16/32 Ab (BD Pharmingen) to prevent nonspecific Ab binding to FcγRs on APCs. For analysis of cellular subsets in peripheral blood, spleen, lymph nodes and bronchoalveolar lavage, markers used in conjunction with FcRn staining were anti-CD45-FITC, anti-CD11b-PE, anti-CD11c-FITC, anti-B220-FITC, anti-CD3ε-PE, anti-Gr1-FITC, anti-Thy1.1-FITC, and Thy1.2-PE (all from BD Pharmingen). Stained single-cell suspensions from FcRn wild-type or knockout mice were analyzed in parallel on FACScan or FACSCalibur systems (BD Biosciences).

Tissue sections were fixed with ice-cold acetone for 5 min and then allowed to air dry for 10 min. Tissue patches were encircled with a PAP pen (RPI Corporation) to generate a hydrophobic barrier. Sections were blocked with 10% BSA in PBS for at least 30 min. FcRn staining was performed using a 1/500 dilution of antiserum in blocking buffer. Vascular endothelium was detected using a 1/200 dilution of anti-PECAM-1 Abs (eBioscience or BD Pharmingen). Basal keratinocytes were detected with a 1/10,000 dilution of anti-keratin-14 Ab (Covance). Hemopoietic cells in the lung were detected with a 1/200 dilution of anti-CD45-FITC (BD Pharmingen). Macrophages in tissues were detected with a 1/100 dilution of anti-CD11b-FITC or anti-F4/80-FITC (both from BD Pharmingen). Before staining for APCs, sections were preincubated for 15 min with a 1/100 dilution of anti-CD16/32 Ab (BD Pharmingen) to prevent nonspecific Ab binding to FcγRs on APCs. Stained tissue sections were coverslipped in ProLong antifade reagent (Molecular Probes) and were imaged using a Zeiss Axiovert 100M microscope system using a ×63 (1.4 NA) oil immersion objective.

Bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC) were obtained by flushing bone marrow from the femurs and tibias of mice. For macrophages, cells were cultured for 7 days in L cell-conditioned medium in 10% FCS-supplemented DMEM on bacterial petri dishes (non-tissue culture treated). Cells were washed once in calcium and magnesium-free PBS and then scraped off in PBS using a rubber policeman. Cultured BMDM were >90% CD11b⁺. For dendritic cells, bone marrow cells were cultured in 10% FCS-supplemented RPMI 1640 with GM-CSF-conditioned supernatant (a gift from M. Cella and M. Colonna, Washington University School of Medicine, St. Louis, MO). Nonadherent and slightly adherent cells were collected on day 7 and dendritic cells were enriched to >90% purity (CD11b⁺CD11c⁺) on a 14.5% w/v Histodenz gradient (Sigma-Aldrich).

HEK293 cells were cultured in 5% FCS containing DMEM. Cells were stably transfected with GFP-tagged FcRn (mouse or human) using FuGENE6 reagent according to the manufacturer’s protocol. Stable transfectants were selected and maintained in culture medium containing 1 mg/ml G418 (Invitrogen Life Technologies).

HEK293 cells and stable transfectants were plated onto poly-l-lysine (Sigma-Aldrich) treated coverslips in a 6-well plate in appropriate culture medium. Cells were washed once with PBS and fixed for 10 min in 1% PFA in PBS. Cells were washed and then blocked/permeabilized with 1% BSA 0.5% saponin in PBS. FcRn was stained with a 1/500 dilution of antiserum and detected with anti-hamster IgG-Cy5 (Jackson ImmunoResearch Laboratories) in blocking buffer. After each staining step, unbound Ab was washed with PBS plus 0.5% saponin. Coverslips were mounted in ProLong antifade reagent (Molecular Probes) and imaged as described above.

Images were captured at room temperature using Zeiss LSM510 software and were exported as TIFF images. Images were assembled in Adobe Photoshop. The only image manipulations performed were occasional cropping and linear brightness/contrast adjustments that were applied evenly across images from control and experimental samples. Image quantitation was performed using ImageJ software (25) as described previously (26). Briefly, for colocalization analysis, structures were outlined using ImageJ and the mean fluorescence intensity of at least five marker-positive structures (m) was corrected and normalized to background (b) using the formula (m − b)/b. The ratio of FcRn staining to marker staining was then computed for each outlined structure. The individual ratios between FcRn wild-type and knockout images were then compared using a two-tailed Student t test. Comparisons resulting in p < 0.05 were considered as evidence for positive colocalization.

Groups of 10–12 6-wk-old recipient mice were lethally irradiated (10 Gy) and were transplanted i.v. via the tail vein with 7.5 × 10⁶ bone marrow cells. In one experiment, B6.PL-Thy1^a/CyJ (Thy1.1) mice were used as donors or recipients to track the degree of chimerism in reconstituted animals using the Thy1 marker (FcRn^−/− mice are on the C57BL6/J background and express Thy1.2). After the bone marrow transplant, mice were allowed free access to water containing trimethoprim/sulfamethoxazole for 3 wk before being switched to antibiotic-free water. Sixteen weeks after reconstitution, 100 μg each of monoclonal anti-TNP-specific IgG (mAb 1B7.11) and IgA (mAb 2F.11.15) tracers were injected i.p. (day −1). On subsequent days (0, 1, 2, 4, and 6), mice were bled via the retro-orbital sinus (50–75 μl) and serum was collected. The amount of tracer was quantitated by ELISA against a standard curve as described previously (3). For each mouse, the amount of tracer present at day 0 was set at 100% and the amount of tracer remaining on subsequent days was expressed as a fraction of the amount present on day 0. Values were compared using the two-tailed Student t test. Because we made three comparisons (WT→WT vs KO→WT; KO→WT vs WT→WT; WT→WT vs KO→KO), we applied the Bonferroni correction and considered p values <0.0167 (0.05/3) as significant.

We immunized Armenian hamsters with mouse cells transfected with a truncated form of FcRn lacking the cytoplasmic tail. This allowed FcRn to be expressed at high levels on the plasma membrane (27). After immunization, we tested antisera for mouse and human FcRn reactivity by flow cytometry and confocal microscopy. By flow cytometry, the antiserum recognized human FcRn weakly but was highly reactive against mouse FcRn (Fig. 1,A). When we stained cells expressing GFP-tagged human or mouse FcRn, the antiserum preferentially stained mouse FcRn although there was weak background staining in untransfected cells (Fig. 1,B). Because FcRn is highly expressed in the proximal small intestine of neonatal rodents, we stained sections of small intestine from 10-day-old mice. The antiserum recognized FcRn expressed in these tissue samples with strong FcRn expression in the enterocyte cytoplasm and on the intestinal brush border (Fig. 1 C). The pattern was specific because no staining was detected in small intestine from FcRn-deficient animals. No specific staining was observed with either preimmune serum or secondary only controls (data not shown). Lastly, adsorption of the antiserum on cells expressing FcRn eliminated specific staining (data not shown).

To examine FcRn expression in the vascular endothelium of various organs, sections from various tissues were costained for FcRn and PECAM-1, a marker of endothelial cells. Because the vascular endothelium of skin and skeletal muscle are proposed to be the sites at which FcRn protects serum IgG from degradation, we first examined these tissues (15). Consistent with previous reports, we found that FcRn was expressed at high levels in the vasculature of these organs (Fig. 2, A and B). There were, however, differences in the staining patterns between skin and muscle. Although FcRn expression in skeletal muscle was limited to endothelial cells, FcRn had a broader pattern of expression in the skin. In addition to the endothelium, FcRn was highly expressed by cells with a dendritic or macrophage-like morphology in the dermis (see below). The stratum corneum and epidermis of mouse skin also stained weakly with the antiserum (Fig. 3 A), consistent with a previous report (28). However, this staining was nonspecific as a similar pattern of staining was seen in FcRn knockout skin.

The vascular endothelium in different parts of the body is variably permeable to serum molecules. This led to the concept of barrier endothelium in the vasculature of organs such as the brain (29), testes (30), and thymus (31). The blood-brain barrier consists of cerebral capillaries and the choroid plexus ependyma and excludes IgG from the brain parenchyma and cerebrospinal fluid (32). Consistent with a previous report, we detected high levels of FcRn in the cerebral vasculature and choroid plexus (Fig. 2 C) (33). We did not detect FcRn in neurons, astrocytes, or microglia. This suggests that FcRn might play a role in maintaining the blood-brain barrier.

We also examined testes and thymus. In the testes, the blood-tissue barrier exists at the level of the tight junctions between the Sertoli cells (30). The pattern of FcRn expression in the PECAM-positive testicular vasculature was not significantly different between wild-type and knockout tissues (data not shown). However, several smaller structures (possibly PECAM-1-negative capillaries) in the interstitium stained strongly for FcRn. No FcRn expression was detected within the seminiferous tubules. In the thymus, the endothelial cells of the cortex exclude blood-borne Ags from entering the thymus. Similar to the testes, we did not detect FcRn expression in cortical or medullary blood vessels of the thymus (data not shown).

The lung and kidney are highly vascularized and have specialized epithelial barriers active in gas and electrolyte exchange. Given that the lung has a large vascular bed and receives 100% of the cardiac output, we were surprised to find no significant FcRn expression in the lung microvasculature or pneumocytes (data not shown). Although a few interstitial cells expressed high levels of FcRn, we did not observe FcRn expression in the bronchiolar epithelium in contrast to previous reports (Fig. 3 B) (34, 35).

Previous studies reported FcRn expression in the glomerular epithelial cells (podocytes) and the proximal convoluted tubule brush border (21). FcRn expression in the glomerulus was not interpretable due to high background staining of the mesangium present in both the wild-type and FcRn knockout kidney. However, we confirmed previous reports of FcRn expression in podocytes (21) by immunoblotting FcRn in cultured podocytes (data not shown). FcRn was, however, highly expressed in the tubular system in a proximal to distal gradient with the proximal convoluted tubule (especially the S1 segment) expressing the highest levels (Fig. 3 C). In contrast to a previous report (21), most of the staining in the proximal tubule was in the cytoplasm with no enrichment in the brush border.

In the neonatal rodent, high FcRn expression has been reported in the proximal small bowel with a progressive decrease in expression along the length of the intestine (36). A recent report found that FcRn transcript is expressed in the murine adult small intestine (37). In our studies, we detected FcRn in the duodenal epithelium (Fig. 3,D) but not in any cells of the stomach, ileum, or colon from adult animals (data not shown). In the duodenum, the staining was mainly of the cell body and not enriched at the brush border as seen in the neonate (Fig. 1 C). Costaining with PECAM-1 showed little colocalization with FcRn in the gut. In contrast to a previous report using human tissues, we did not detect FcRn expression in colonic enterocytes or lamina propria cells (data not shown) (38).

Although FcRn expression has been reported in hepatocytes (19) and hepatic sinusoidal cells (15), expression in other organs of the reticuloendothelial system were not examined. We confirmed strong FcRn staining in the sinusoidal cells of the liver (Fig. 4 A). In some tissue sections, we also detected FcRn staining in the endothelium of the central veins but we did not observe FcRn expression in the portal vessels. This staining pattern differs slightly from a previous report in which FcRn was not detected in the central vein or the portal vasculature (15). In addition to the vasculature, Kupffer cells (expressing F4/80) also stained strongly for FcRn and weak staining was detected in the hepatocytes themselves.

Next, we stained spleen and lymph node sections for FcRn. In the spleen, FcRn was most highly expressed in the red pulp. Strong FcRn expression was detected in the sinusoids of the red pulp, but not in the majority of the red pulp macrophages (Fig. 4,B). A few cells with macrophage-like morphology in the marginal zone and neighboring red pulp labeled strongly for FcRn. The white pulp was devoid of FcRn expression except for weak staining in the marginal sinus endothelium. Consistent with data reported in human lymphocytes (39), we confirmed that murine B and T cells did not express FcRn by flow cytometry (data not shown). In the lymph node, we detected high levels of FcRn staining in the subcapsular sinus macrophages and macrophage-like cells in the interfollicular areas of the lymph node cortex (Fig. 4 C). Similar to the spleen, little FcRn expression was detected in the B cell areas of the cortex. In the medulla, FcRn expression was detected in scattered cells with macrophage-like morphology.

Our examination of FcRn expression in the skin, liver, lung, spleen, and lymph nodes suggested that FcRn was expressed in professional APCs. This was confirmed in the skin by costaining sections for FcRn and the macrophage marker CD11b (Fig. 5,A) or MHC class II (data not shown). In the lung, costaining with the macrophage markers CD45 and CD11b confirmed FcRn expression in alveolar macrophages (Fig. 5,B, data not shown). Analysis of alveolar macrophages retrieved using bronchoalveolar lavage (BAL) confirmed that CD45⁺- or CD11b⁺-positive alveolar macrophages expressed high levels of intracellular FcRn (Fig. 5 C, data not shown).

Using flow cytometry, we confirmed that CD11b⁺ cells from peripheral blood, spleen, and lymph node expressed FcRn (Fig. 5,C). Notably, FcRn expression was not uniform in these APC populations. Although the entire population of CD11b⁺ alveolar macrophages expressed high levels, FcRn expression was more heterogeneous in the splenic and lymph node CD11b⁺ population. Lastly, cultured BMDM and dendritic cells also demonstrated FcRn expression (Fig. 5 C).

It is widely assumed that FcRn expression in endothelial cells is mostly responsible for maintaining the long serum half-life of IgG. To test whether FcRn expression in APCs also played a role, congenically marked wild-type or FcRn knockout bone marrow was transplanted into groups of lethally irradiated recipient wild-type or FcRn-deficient mice. This allowed us to separate the contribution of endothelial cells from the contribution of APCs. Analyzing T cells, we confirmed that chimerism was >90% in all transplanted mice (data not shown). Leukocyte subset analyses of chimeric mice confirmed that they had equivalent numbers of B cells, T cells, monocytes, and neutrophils (data not shown). We also confirmed FcRn expression in the peripheral blood Mac1⁺Gr1⁻ mononuclear cells of chimeric mice (Fig. 6 A) and verified that they had the donor pattern of FcRn expression.

Injection of a monoclonal IgG tracer was then used to measure IgG half-life (3). Although wild-type bone marrow transplanted into wild-type mice had a half-life of 5.2 ± 0.9 days, knockout bone marrow transplanted into knockout mice had a much shorter half-life of 1.3 ± 0.1 days (Fig. 6,B, Table I). The important role of APCs in regulating IgG homeostasis was shown by the decreased half-life of 2.8 ± 0.7 days when knockout bone marrow was transplanted into wild-type mice. The contribution of non-bone marrow-derived cells was shown by the decreased half-life of 2.3 ± 0.3 days when wild-type bone marrow was transplanted into knockout mice. As expected, all transplanted groups of mice rapidly cleared the IgA tracer, which does not have a known protection receptor. This demonstrates that FcRn expression in bone marrow-derived cells plays a significant role in regulating IgG serum half-life.

In this study, we demonstrate that FcRn is broadly expressed in many APC subsets. In addition, we have shown that FcRn expressed in APCs extends the serum half-life of IgG. Thus, both endothelial cells and bone marrow-derived APCs express FcRn and contribute to IgG homeostasis.

In adult animals, FcRn functions as the IgG homeostatic receptor by extending the serum half-life of IgG Abs. In cells that are in contact with serum, random internalization of serum proteins would result in high rates of serum protein catabolism. Because of the presence of FcRn, which recycles internalized IgG to the cell surface, IgG has a much longer half-life than most serum proteins. Because of its large contact area with the serum, the vascular endothelium is proposed to be the major site of FcRn expression (15). Our studies confirm previous reports that the large vascular beds of skin and skeletal muscle express FcRn (15). Although FcRn was highly expressed in the vasculature of skin, muscle, liver, and spleen, FcRn expression was not detected in the pulmonary and enteric vasculature. This regional variability of FcRn expression in the vasculature underscores the heterogeneity of the endothelium and also suggests that FcRn may have specific roles at different sites.

Even though the mouse is the most commonly used mammalian model organism, the tissue expression pattern of FcRn expression in mouse had not been previously examined. Most published studies used rat or human tissues (19, 21, 22, 28, 33, 34, 40, 41). The availability of FcRn-deficient animals (3) allowed us an important control for staining specificity. This allowed us to comprehensively document FcRn expression in most tissues in the mouse. We confirmed most of our staining results with publicly available data from tissue microarrays (data not shown).

Our studies demonstrate that FcRn is expressed in a variety of different professional APCs. Professional APCs comprise a heterogeneous population of cells that functions in the initiation of adaptive immune responses. A previous report demonstrated FcRn expression in primary human monocytes, intestinal macrophages, and macrophage cell lines (39), and speculated that it may play a role in serum IgG homeostasis. Because APCs exhibit high levels of phagocytosis and macropinocytosis (42, 43, 44), we hypothesized that FcRn expressed in APCs might function similarly to endothelial cells and recycle internalized IgG. To test this idea, we performed reciprocal bone marrow chimera experiments using FcRn wild-type and knockout mice. This allowed us to compare the relative contributions of endothelial cells to bone marrow cells in serum IgG preservation. These experiments demonstrated that both hemopoietic and nonhemopoietic components play roles in the maintenance of IgG levels in the blood. Although it is difficult to ascribe exactly the contribution of the hemopoietic cell population to IgG homeostasis, the bone marrow chimera experiments demonstrate that it plays a significant role, at a level that is potentially similar to the role of endothelial cells. FcRn expressed at other sites may also extend the half-life of serum IgG as suggested for FcRn expressed in the mammary gland (45). Taken together, however, our results suggested that bone marrow-derived cells and vascular endothelial cells are major cell types responsible for the FcRn-dependent extension of serum IgG half-life.

FcRn also functions to maintain total IgG levels in the mouse. FcRn and β₂-microglobulin-deficient mice both exhibit ∼10% of the level of serum IgG as wild-type animals (3, 9). We tested our bone marrow chimeric animals to see whether bone marrow FcRn contributed to maintaining normal resting levels of IgG. Unfortunately, the range of resting IgG levels in wild-type animals reconstituted with wild-type bone marrow was so wide as to make the interpretation of the other bone marrow combinations uninterpretable. Although the level of chimerism of our experimental animals was high, we suspect that the variability of IgG levels is due to variability of IgG production after bone marrow reconstitution in these animals.

It is interesting to speculate that FcRn may have other functions in APCs in addition to the preservation of IgG. Because FcRn binds most strongly in the acidic environment of endosomes, it seems possible that FcRn could be involved in the intracellular trafficking of immune complexes. A recent study reported that dendritic cells internalize IgG immune complexes bound to their cell surface FcγRs and can recycle intact Ag back to the cell surface (46). FcRn might be a good candidate to explain how this trafficking occurs.

In summary, we have described the tissue distribution of FcRn in the adult mouse. Consistent with previous reports, we found FcRn to be highly expressed in vascular endothelium but with some regional variability from tissue to tissue. FcRn was also expressed at some barriers (brain, testes), but not others (thymus), which potentially highlights differences in the composition and maintenance of blood-tissue barriers to IgG. Lastly, FcRn was expressed in several different types of professional APCs where it contributed significantly to extending the half-life of serum IgG. The possible role of this transport receptor in these cells that are responsible for the initiation of the adaptive immune response is the topic of future studies.

The authors have no financial conflict of interest.