The article published by Mohr et al. in the February 15, 2009 issue of The Journal of Immunology (1) characterizes the cells in mouse lymph nodes that produce a proliferation-inducing ligand (APRIL) from the TNF superfamily, a key factor in the differentiation/survival of plasmablasts/plasmocytes. Mohr et al. report that monocytes/macrophages, characterized by a Gr-1low/F4/80+ surface phenotype, are one of the main sources of APRIL in a lymph node draining an immunization site, while Gr-1high neutrophils are a minor source. This contrasts significantly from what we have observed in the human system where neutrophils are the main cellular sources of APRIL in mucosa-associated lymphoid tissues and bone marrow (2, 3). However, it is consistent with our study in mouse bone marrow showing that Gr-1low/Mac-1+ resident macrophages are much more superior in APRIL production that GR-1high/Mac-1 neutrophils (Ref. 4 and unpublished data). To further document APRIL production mouse and human, we are now reporting that neutrophils also mediate most of the APRIL production in human lymph nodes. Indeed, the Stalk-1 Ab, which detects cells producing APRIL (3), stained cells with a similar localization in lymph nodes as cells expressing the neutrophil marker elastase (Fig. 1), and with a characteristic segmented nucleus of human neutrophil. Taken together, these four studies highlight a major difference in APRIL production in the mouse versus the human system. Gr-1low macrophages are the major source of APRIL in mouse, while it is elastase+ neutrophils in human.

FIGURE 1.

Neutrophils produce APRIL in human lymph nodes. A and B, A human lymph node was stained with Stalk-1, detecting cells producing APRIL (A) and elastase, a marker of neutrophils (B). Original magnification was ×20. C, Higher magnification (×63) is shown for a Stalk-1-stained cell. We took the picture out of focus to highlight the segmented nucleus.

FIGURE 1.

Neutrophils produce APRIL in human lymph nodes. A and B, A human lymph node was stained with Stalk-1, detecting cells producing APRIL (A) and elastase, a marker of neutrophils (B). Original magnification was ×20. C, Higher magnification (×63) is shown for a Stalk-1-stained cell. We took the picture out of focus to highlight the segmented nucleus.

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1
Mohr, E., K. Serre, R. A. Manz, A. F. Cunningham, M. Khan, D. L. Hardie, R. Bird, I. C. MacLennan.
2009
. Dendritic cells and monocyte/macrophages that create the IL-6/APRIL-rich lymph node microenvironments where plasmablasts mature.
J. Immunol.
182
:
2113
-2123.
2
Huard, B., T. McKee, C. Bosshard, S. Durual, T. Matthes, S. Myit, O. Donze, C. Frossar, C. Chizzolini, C. Favre, et al
2008
. APRIL secreted by neutrophils binds to heparan sulfate proteoglycans to create plasma cell niches in human mucosa.
J. Clin. Invest.
118
:
2887
-2895.
3
Schwaller, J., P. Schneider, P. Mhawech-Fauceglia, T. McKee, S. Myit, T. Matthes, J. Tschopp, O. Donze, F. A. Le Gal, B. Huard.
2007
. Neutrophil-derived APRIL concentrated in tumor lesions by proteoglycans correlates with human B-cell lymphoma aggressiveness.
Blood
109
:
331
-338.
4
Belnoue, E., M. Pihlgren, T. L. McGaha, C. Tougne, A. F. Rochat, C. Bossen, P. Schneider, B. Huard, P. H. Lambert, C. A. Siegrist.
2008
. APRIL is critical for plasmablast survival in the bone marrow and poorly expressed by early-life bone marrow stromal cells.
Blood
111
:
2755
-2764.