CD40 EXPRESSION AND FUNCTION IN MURINE B-CELL ONTOGENY

The CD40 antigen, a member of the nerve growth factor/tumor necrosis f actor receptor family, is expressed on all mature B lymphocytes and pl ays a crucial role in B cell activation, T cell-dependent antigen-driv en isotype switching and germinal center formation, We have analyzed C D40 expression and function during mouse B cell development by examini ng B cell precursors in normal mice and in transgenic animals in which B cell development is frozen at discrete stages, These models include d RAG-2(-/-) mice, and transgenic littermates that express a mu heavy chain and/or the bcl-2 proto-oncogene transgene, CD40 was undetectable at the pro-B cell stage, but was expressed, although at low levels, o n pre-B cells, However, pre-B cells failed to respond to CD40 triggeri ng either by expression of CD23 or by proliferation in the presence of IL-4. Overexpression of bcl-2 increased the density of CD40 expressio n on pre-B cells: these cells respond to CD40 ligation by expressing C D23 and by proliferating in the presence of IL-4.