GAMMA-2B PROVIDES ONLY SOME OF THE SIGNALS NORMALLY GIVEN VIA MU IN B-CELL DEVELOPMENT

B cell development is a complex process involving interactions between B cell precursors, stroma, and known and unknown ligands and cytokine s. In order to more fully understand the requirements for Ig in that d evelopment we have created transgenic mice that carry a gamma 2b trans gene and express it early in B cell development, Previously it was bel ieved that these B cells arrested in their development prior to the pr o- to pre-B cell transition. We show here that in conventional gamma 2 b mice, B cell development actually arrests later, at the pre-B cell s tage, This shows for the first time that a constant region different f rom mu can allow signaling through the pre-B cell receptor, but cannot promote complete development, The pro- and pre-B cells in the convent ional gamma 2b transgenics are not fully functional since they cannot grow in IL-7 without stromal cells, This is a novel phenotype, separat ing development from stroma independence, The few, mature B cells that do develop in these mice express both mu and gamma 2b simultaneously, and are CD5(+). Expression of a Ecl-2 transgene allows survival of ga mma 2b transgenic immature B cells, but does not promote full maturati on, indicating that normally mu provides both an anti-apoptotic signal and a differentiation signal. One line of gamma 2b mice, the C line, does not have this phenotype, B cell development is accelerated in thi s unconventional line, and the developing B cells have a very differen t phenotype from both normal mice and conventional gamma 2b mouse line s, but are very similar to mu transgenics, Mature B cells are largely CD5(-), gamma 2b-only expressing, This unique phenotype is apparently due to the activation in B cell precursors of a gene at the insertion site of the transgene, circumventing the need for mu. Comparison of co nventional gamma 2b transgenics with the C line and mu transgenics rev eals the multiple signals required throughout B cell development.