CD40-ACTIVATED SURFACE IGD-POSITIVE LYMPHOCYTES CONSTITUTE THE LONG-TERM IL-4-DEPENDENT PROLIFERATING B-CELL POOL

In vitro, B cells undergo long term proliferation when triggered throu gh their CD40 surface molecule and in the presence of IL-4. Here, we s how that cells that proliferate in this culture system lose their germ inal center (GC) features and acquire or maintain non-GC markers. When separated by the magnetic cell separation system, both sIgD+ and sIgD - B cells can proliferate in this culture system, sIgD+ B cells exhibi ting a higher rate of growth than sIgD- cells. Simultaneous flow cytom etric measurement of sIgD and DNA content revealed that B lymphocytes can keep their sIgD after entry into cell cycle. Experiments using G8 Id-positive B lymphocytes allowed us to follow the evolution of sIgDand sIgD- cells in a reconstituted B cell population. Long term prolif erating cells are sIgD+/sIgM+-derived B lymphocytes whereas the initia l sIgD-/sIgM- cells are lost. Taken together, these data show that ant i-CD40+IL-4 activated sIgD+ B blasts express non-GC characteristics an d that sIgD+ B cells preferentially proliferate in the CD40 system. Th e possible in vivo role of IL-4+CD40 signaling is discussed.