Positive and negative roles of the tyrosine kinase Lyn in B cell function

The function of Lyn in B cell activation has been studied recently by examining the properties of B cells from mice in which thelyngene has been inactivated by gene targeting. These mice show evidence of B cell hyperreactivityin vivo,as the number of B lymphoblastoid cells greatly increase with age, IgM levels increase by 10-fold or more, and auto- antibodies to double-stranded DNA and other nuclear antigens become apparent. B cells fromlyn−/−mice also exhibit enhanced BCR-induced activation of MAP kinases, intracellular calcium elevation and proliferative responsesin vitro.Thes e phenomena may relate to participation of Lyn in events that serve to decrease B cell responses to antigen. Among the leading candidates for these suppressive events are the inhibition of B cell antigen receptor function by FcγRIIb1 and by CD22. Although Lyn also participates positively in the initial events of B cell antigen receptor signal transduction, this function can also be supplied by other tyrosine kinases, presumably other Src-family kinases. In contrast, some aspects of inhibition by CD22 appear to be almost completely dependent upon Lyn and FcγRIIb1 inhibition is also diminished in the absence of Lyn. Thus, the net effect of Lyn action is negative rather than positive for B cell activation.