- MN 410
The activation of naive B cells is a multi-step process that is initiated by binding of specific antigen to the B cell antigen receptors (BAR). Although occupancy of BAR by antigen serves to select B cell clones for inclusion within the developing humoral immune response, under most circumstances the biochemical signals emanating from such occupied receptors are not sufficient to drive resting B cells through the cell cycle. To elicit the complete activation of antigen-reactive B cells typically requires a physical interaction between the B cell and an antigen-specific, fully activated T helper (Th) cell. Partially activated B cells can revert back to the resting state, or become either anergic or apoptotic, and the path selected depends on the extent of signals delivered. B cells that are successfully stimulated to undergo expansion require continued delivery of signals through either their BCR or via interactions with Th cells in order to survive. It is currently thought that these life and death decisions are made as cells progress through the G1 cell cycle stage. Our laboratory studies the biochemical and molecular processes involved as either newly activated or cycling B cells determine their ultimate fate as they pass through the G1 stage of the cell cycle. In addition, certain types of transformed B cells, such as B cell lymphomas, require signals from normal, nontransformed Th cells to both survive and proliferate. Current experiments seek to more fully understand how normal regulatory cells control the growth and survival of such transformed B cells.
Roberts, T., and Snow, E. C. Cutting Edge: Recruitment of the CD19/CD21 coreceptor to B cell antigen receptor is required for antigen-induced expression of Bcl-2 by resting and cycling hen egg lysozyme transgenic B cells. J. Immunol. 162:4377, 1999
Pittner, B. T., and Snow, E. C. Strength of signal through BCR determines the fate of cycling B cells by regulating the expression of the Bcl-2 family of survival proteins. Cell. Immunol. 186:55, 1998
Pittner, B. T., Mullins, M. W., Reid, S., and Snow, E. C. An in vitro approach for the characterization of the cycling B cell response. In vitro Cell. Dev. Biol. 34:421, 1998
Mullins, M. W., Pittner, B. T., and Snow, E. C. CD40-mediated induction of p21 accumulation in resting and cycling B cells. Mol. Immunol. 35:567, 1998