CROSS-LINKING OF ANTIGEN RECEPTOR VIA IG-BETA (B29, CD79B) CAN INDUCEBOTH POSITIVE AND NEGATIVE SIGNALS IN CD40-ACTIVATED HUMAN B-CELLS

Antigen-dependent activation of B lymphocytes is mediated through surf ace immunoglobulins and their associated molecules Ig-alpha (CD79a, Mb 1) and Ig-beta (CD79b, B29). Here we show that an antibody directed ag ainst the extracellular part of human Ig-beta can, when cross-linked b y CD32-transfected L cells, induce an IL-2-dependent proliferation of tonsil B cells. With the use of L cells stably transfected with both C D32 and CD40L, anti-Ig-beta activation of B cells was combined with CD 40 triggering, an important component of the T cell-dependent B cell a ctivation. This dual cellular activation resulted in two different pha ses, with initially synergistic proliferative effects, both without an d with IL-2 or IL-10. Then, after 5-6 days of culture, cells stimulate d with both anti-Ig-beta and CD40L underwent massive cell death, in co ntrast to B cells activated with CD40L alone. Cell death was not preve nted by the addition of IL-2 or IL-10, but was prevented by the additi on of Il-4. These results are discussed in the context of positive and negative selection of mature B cells.