Our goal is to identify these selective forces, to determine when they act during differentiation, and to elucidate their mechanisms. The achievement of these goals is feasible with the emergence of exciting new technologies to manipulate the mouse genome in precise ways.
Positive selection occurs at multiple stages and is essential for B cell differentiation.
Our work suggests that pre-B cell survival in the bone marrow depends on the transmission of a signal from the heavy chain receptor on the cell surface initiated by ligand binding. Current efforts are aimed at testing this hypothesis and elucidating the mechanism of positive selection. B cell positive selection also occurs at mature stages. There are numerous mature B cell subsets in mice and man, and each has a different function in the immune system. Recent evidence of ours suggests that B cells segregate into these different subsets as a function of their antigen specificity by a positive selection mechanism.