Immune responses to bacterial capsular polysaccharides involve antibody responses by B cells activated via surface Ig receptors. B cells activated by Ig cross-linking undergo an ordered chain of events. These events include stimulation of kinase activity, gene and nuclear factor activation, and entry into cell cycle. Mice with the x-linked immunodeficiency gene (xid) are believed to possess a mutation in the pleckstrin homology domain of Bruton's tyrosine kinase (Btk). These animals are unresponsive to polysaccharide antigens, moreover their B cells do not proliferate after Ig cross-linking, although they do enlarge. To determine at which point in the activation pathway xid cells become arrested, both early and late events are being compared in sIg activated xid and wildtype B cells. We have found that early G1 events, such as nuclear factor and proto-oncogene induction occur in xid cells normally. Furthermore, the activity of src related kinases was equivalent in xid and wildtype cells. However, induction of cell cycle associated events did not occur in xid cells. A clear understanding of the events associated with sIg mediated activation is required to optimize immune responses to polysaccharide vaccines because these antigens have the ability to trigger B cells directly. This understanding is especially important for vaccination of very young and elderly populations which respond poorly to polysaccharides.
