Differential Endotoxin Sensitivity of Lymphocytes and Macrophages from Mice with an X-Linked Deffect in B Cell Maturation¹

The in vitro sensitivity of B lymphocytes and macrophages derived from (CBA/N × DBA/2N) F₁ male mice, which carry an X-linked recessive gene that produces defective B cell maturation, was compared to phenotypically normal F₁ female mice. B lymphocytes of F₁ males exhibit an abnormal mitogenic response to LPS in serum-free culture conditions, which is partially reversed in the presence of serum. In contrast, both resident and thioglycollate-induced peritoneal macrophages of F₁ male mice respond normally to LPS. In response to LPS in vitro, F₁ male macrophages produce the monokine, lymphocyte-activating factor (LAF) and release prostaglandins. Furthermore, F₁ male macrophages are sensitive to the lethal effects of LPS. Therefore, the defective CBA/N gene appears to be expressed only in B lymphocytes and not in macrophages. Since F₁ male mice are normally sensitive to the lethal and adjuvant effects of LPS in vivo, these findings suggest that a mature B lymphocyte population is not required for these effects and support the role of the macrophage in the mediation of LPS-induced lethality and adjuvanticity.