Murine B1B cells require IL-5 for optimal T cell-dependent activation

T helper cell-driven activation of murine B cells has been shown to depend upon CD40-CD40 ligand (CD40L) interactions and a defined set of cytokines, These observations are primarily based on the use of conventional B cells o btained from the spleen. Therefore, it is presently unclear whether all mat ure B cell subsets found in the mouse have an equal dependence upon CD40-CD 40L interactions and use the same T cell-derived cytokines, The present stu dy tested the response of splenic follicular and marginal zone as well as p eritoneal B2 and B1 B cells to Th cell stimulation. Splenic and peritoneal B cell subsets were sort purified based on CD23 expression, and cultured wi th rCD40L and cytokines or Th2 cells, The results demonstrate that follicul ar, marginal zone, and peritoneal B2 B cells require CD40-CD40L interaction s and preferentially use IL-4 for optimal proliferation, differentiation, a nd isotype switching. In contrast, peritoneal B1 B cells use IL-5 in conjun ction with CD40-CD40L interactions for maximal Th cell-dependent responses. Furthermore, B1 B cells are capable of proliferating, differentiating, and isotype switching in the absence of CD40-CD40L interactions. B1 B cells ar e able to respond to Th2 clones in the presence of anti-CD40L mAb as well a s to Th2 clones derived from CD40L(-/-) mice. The CD40-CD40L-independent re sponse of B1 B cells is attributable to the presence of both IL-4 and IL-5, and may explain the residual Ab response to T cell-dependent Ags in CD40L- or CD40-deficient mice, and in X-linked hyper-IgM (X-HIM) patients.