Analysis of signaling via surface immunoglobulin receptors on b cells from cba/n mice

Abstract

CBA/N mice, which carry the xid immunodeficiency, lack a mature subpopulation of B cells. The residual B cells in these mice do not make antibodies to type‐2 T‐independent antigens, nor do they synthesize DNA in response to mitogenic forms of anti‐Ig antibodies. It is therefore an attractive hypothesis that the surface immunoglobulin receptors (sIgR) on xid B cells signal abnormally following cross‐linking. We show here that anti‐Ig antibodies do cause inositol phospholipid hydrolysis and Ca²⁺ mobilization in xid B cells. However, the responses of these cells are only 40%–50% of those of normal B cells. Studies with permeabilized cells demonstrated that the hyporesponsiveness is not due to ineffective coupling of sIgR to their associated G‐protein. Rather it is apparently due to a quantitative and/or qualitative deficiency in the polyphosphoinositide‐specific phosphodiesterase which mediates sIgR‐induced inositol phospholipid hydrolysis. These observations may provide a biochemical explanation for the immunological abnormalities resulting from the xid mutation.