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 the lyn gene ha s been inactivated by gene targeting. These mice show evidence of B ce ll hyperreactivity in vivo, as the number of B lymphoblastoid cells gr eatly increase with age, IgM levels increase by IO-fold or more, and a utoantibodies to double-stranded DNA and other nuclear antigens become apparent. B cells from lyn(-/-) mice also exhibit enhanced BCR-induce d activation of MAP kinases, intracellular calcium elevation and proli ferative responses in vitro. These phenomena may relate to participati on of Lyn in events that serve to decrease B cell responses to antigen . Among the leading candidates for these suppressive events are the in hibition of B cell antigen receptor function by Fc gamma RIIb1 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 ki nases. In contrast, some aspects of inhibition by CD22 appear to be al most completely dependent upon Lyn and Fc gamma RIIb1 inhibition is al so diminished in the absence of Lyn. Thus, the net effect of Lyn actio n is negative rather than positive for B cell activation.