B cells from CBA/N mice do not proliferate following ligation of CD40.
The CBA/N mouse carries the X-linked immunodeficiency xid, resulting in defective B cell development. B cells from these animals cannot mount antibody responses to type 2 T-independent antigens, and do not synthesize DNA when stimulated with anti-immunoglobulin (Ig) antibodies which are mitogenic for normal B cells. The primary antibody responses of CBA/N mice to T-dependent antigens have also been reported to be abnormal. Here we describe the results of experiments which demonstrate that the B cells from these animals respond abnormally to ligation of CD40, a B cell surface molecule now known to play a key role during T cell-B cell interactions, via its interaction with the counterligand (CD40L) expressed by activated T cells. Hence, xid B cells fail to proliferate when cultured with preactivated T helper type 2 (Th2)T cells (known to express CD40L), with a soluble CD40L-CD8 fusion protein, or in response to monoclonal antibodies to CD40, even in the presence of IL-4 and/or anti-Ig reagents. However, xid B cells do receive abortive activation signals following ligation of CD40, as manifested by up-regulation of class II major histocompatibility complex and CD23 antigens. Since the xid defect has now been identified as a point mutation in the protein tyrosine kinase Btk, our results point to an important role for this kinase in the downstream signaling cascade elicited in response to ligation of either surface Ig or CD40.
Hasbold
J
J
National Institute for Medical Research, London, GB.
Klaus
G G
GG
D000818:Animals; D015703:Antigens, CD / Q000502:physiology*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D019013:CD40 Antigens; D023201:CD40 Ligand; D002478:Cells, Cultured; D005260:Female; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008808:Mice, Inbred CBA; D011993:Recombinant Fusion Proteins; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology
D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D019013:CD40 Antigens; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D023201:CD40 Ligand