PHENOTYPIC AND FUNCTIONAL-ANALYSIS OF B-LYMPHOPOIESIS IN INTERLEUKIN-7-TRANSGENIC MICE - EXPANSION OF PRO PRE-B CELL NUMBER AND PERSISTENCEOF B-LYMPHOCYTE DEVELOPMENT IN LYMPH-NODES AND SPLEEN/

Transgenic mice in which mouse interleukin (IL)-7 cDNA is expressed un der the control of the mouse major histocompatibility complex (MHC) cl ass II (E alpha) promoter develop a lymphoproliferative disease charac terized by the early polyclonal expansion of T cells followed in many cases by the development of lymphomas of immature B cells. Here, we ha ve analyzed B cell development in these transgenic mice. Phenotypic an alysis using monoclonal antibodies to B220, IgM, IgD, c-kit, IL-7 rece ptor, MHC class II, AA4.1, CD19, CD23, CD25, CD40 and CD43 shows that B lymphopoiesis in the bone marrow is dramatically altered and the num ber of pro/pre-B and immature B cells is significantly increased. Inte restingly, pro/pre-B and immature B cells persist in the spleens of ad ult transgenic mice and are also present in lymph nodes and blood. Cel l cycle analysis of lymph node cells shows that subpopulations of deve loping B cells retain the cell cycle profiles of their bone marrow cou nterparts. Limiting dilution analysis shows that the number of clonabl e 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 t o decrease between 2 and 4 weeks in control mice with levels in transg enics 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 bone marrow and raise interesting questions re garding the regulation of B lymphopoiesis in normal mice.