Analysis of signaling via surface immunoglobulin receptors on B cells from CBA/N mice.
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 response 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.
Rigley
K P
KP
National Institute for Medical Research, Mill Hill, London.
Harnett
M M
MM
Phillips
R J
RJ
Klaus
G G
GG
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology*; D010712:Phosphatidic Acids / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology; D013873:Thionucleotides / Q000494:pharmacology
D007295:Inositol Phosphates; D010712:Phosphatidic Acids; D011947:Receptors, Antigen, B-Cell; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D010727:Phosphoric Diester Hydrolases; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D002118:Calcium