title: Impaired Ca2+ mobilization by X-linked agammaglobulinaemia (XLA) B cells in response to ligation of the B cell receptor (BCR).
abstract: XLA bone marrow samples were shown to contain B cells expressing IgM, and pre-B cells that express the mu-surrogate light chain (mu psiLC) complex, albeit at a reduced frequency to that found in normal bone marrow. Antibody ligation of mu heavy chain on these cells and an XLA B cell line did not induce a Ca2+ flux, whereas ligation of mu heavy chain on normal bone marrow cells, mu psiLC+ pre-B cell lines and an IgM+ B cell line did. The block in XLA B cells was not due to a defect in the basic mechanism of Ca2+ flux generation, as the cells responded well to thapsigargin. In addition, the defect did not affect T cells, which were shown to respond to CD3 antibody with a Ca2+ flux. Ligation of mu heavy chain on XLA bone marrow cells did, however, activate tyrosine kinases, resulting in tyrosine phosphorylation of a cellular protein with a molecular weight of approximately 115 kD. These results indicate that Btk may be necessary for the generation of the Ca2+ flux in response to ligation of mu heavy chain on B cells and mu psiLC+ pre-B.
authors.affiliation: Immunobiology Unit, Institute of Child Health, London, UK.
authors.forename: H C
authors.initials: HC
authors.lastname: Genevier
authors.forename: R E
authors.initials: RE
authors.lastname: Callard
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002648:Child; D008040:Genetic Linkage; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D014960:X Chromosome
chemical_list: D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D002118:Calcium