Constitutive Bcl-2 expression during immunoglobulin heavy chain-promoted B cell differentiation expands novel precursor B cells.

To test for effects on B cell differentiation, we introduced immunoglobulin mu heavy chain (HC) and Bcl-2 transgenes, separately or together, into recombination-activating gene 2 (RAG-2)-deficient mice. Transgenic Bcl-2 expression led to increased numbers of RAG-deficient pro-B cells, but did not promote their further differentiation. Expression of the mu HC transgene promoted the differentiation of RAG-deficient pro-B cells into pre-B cells that also expressed certain differentiation markers characteristic of even more mature B cell stages. However, the extent of the mu HC-dependent differentiation effects was greatly enhanced by coexpression of the transgenic Bcl-2 gene, and a subset of pre-B cells from both HC and HC, Bcl-2-transgenic RAG-2-deficient animals expressed surface mu HCs that were functional as judged by cross-linking experiments. These experiments demonstrate that the pro-B to pre-B transition in vivo cannot be effected by the expression of Bcl-2 alone, and that nontransformed immature B-lineage cells are competent to receive signals through a surface mu complex.