INFLUENCE OF IMMUNOGLOBULIN HEAVY-CHAIN AND LIGHT-CHAIN EXPRESSION ONB-CELL DIFFERENTIATION

To study the influence of immunoglobulin heavy-chain (HC) and light-ch ain (LC) expression in promoting B-cell differentiation, we have intro duced functional immunoglobulin HC and/or LC transgenes into the recom binase activating gene-2-deficient background (RAG-2(-/-)). RAG-2(-/-) mice do not undergo endogenous V(D)J rearrangement events and, theref ore, are blocked in B- and T-cell development at the early pro-B- and pro-T-cell stages. Introduction of immunoglobulin HC transgenes into t he RAG-2(-/-) background promotes the development of a B-lineage cell population that phenotypically has the characteristics of pre-B cells. We have shown further that this population has altered growth charact eristics as measured by interleukin-7 responsiveness in culture. Bone marrow cells from immunoglobulin HC transgenic RAG-2(-/-) mice have up -regulated expression of germ-line kappa LC gene transcripts and down- regulated expression of lambda(5) surrogate LCs (SLCs). Although mu HC /SLC complexes are detectable intracellularly in HC/RAG-2(-/-) pre-B-c ell populations, HC expression is not readily detectable on the surfac e of these cells. lambda LC RAG-2(-/-) mice had a bone marrow B-lineag e cell phenotype indistinguishable from that of RAG-2(-/-) littermates , indicating that LC expression by itself has no influence on pro-B ce ll differentiation. Strikingly, simultaneous introduction of mu HC and lambda. LC transgenes into RAG-2(-/-) mice led to the generation of a substantial population of ''monoclonal'' peripheral B-cells that were functional with regard to immunoglobulin secretion, indicating that T cells or diverse immunoglobulin repertoires are not necessary for per ipheral B-cell development.