Phenotypic and functional analysis of B lymphopoiesis in interleukin‐7‐transgenic mice: expansion of pro/pre‐B cell number and persistence of B lymphocyte development in lymph nodes and spleen

Transgenic mice in which mouse interleukin (IL)‐7 cDNA is expressed under the control of the mouse major histocompatibility complex (MHC) class II (Eα) promoter develop a lymphoproliferative disease characterized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas of immature B cells. Here, we have analyzed B cell development in these transgenic mice. Phenotypic analysis using monoclonal antibodies to B220, IgM, IgD, c‐kit, IL‐7 receptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43 shows that B lymphopoiesis in the bone marrow is dramatically altered and the number of pro/pre‐B and immature B cells is significantly increased. Interestingly, pro/pre‐B and immature B cells persist in the spleens of adult transgenic mice and are also present in lymph nodes and blood. Cell cycle analysis of lymph node cells shows that subpopulations of developing B cells retain the cell cycle profiles of their bone marrow counterparts. Limiting dilution analysis shows that the number of clonable pre‐B cells is significantly increased and that at limiting dilution, growth of transgenic pre‐B cells is still dependent on exogenous IL‐7. Using semiquantitative polymerase chain reaction (PCR) and in situ hybridization, the level of IL‐7 transcripts in the spleen was found to decrease between 2 and 4 weeks in control mice with levels in transgenics mice being approximately 50 times greater. These transgenic mice represent an interesting model with which to study the effects of IL‐7 overexpression in the bonemarrow and raise interesting questions regarding the regulation of B lymphopoiesis in normal mice.