title: Interference with immunoglobulin (Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation modulates or blocks B cell development, depending on the availability of an Igbeta cytoplasmic tail.
abstract: To determine the function of immunoglobulin (Ig)alpha immunoreceptor tyrosine-based activation motif (ITAM) phosphorylation, we generated mice in which Igalpha ITAM tyrosines were replaced by phenylalanines (Igalpha(FF/FF)). Igalpha(FF/FF) mice had a specific reduction of B1 and marginal zone B cells, whereas B2 cell development appeared to be normal, except that lambda1 light chain usage was increased. The mutants responded less efficiently to T cell-dependent antigens, whereas T cell-independent responses were unaffected. Upon B cell receptor ligation, the cells exhibited heightened calcium flux, weaker Lyn and Syk tyrosine phosphorylation, and phosphorylation of Igalpha non-ITAM tyrosines. Strikingly, when the Igalpha ITAM mutation was combined with a truncation of Igbeta, B cell development was completely blocked at the pro-B cell stage, indicating a crucial role of ITAM phosphorylation in B cell development.
authors.affiliation: Institute for Genetics, University of Cologne, D-50931 Cologne, Germany. kraus@cbr.med.harvard.edu
authors.forename: M
authors.initials: M
authors.lastname: Kraus
authors.forename: L I
authors.initials: LI
authors.lastname: Pao
authors.forename: A
authors.initials: A
authors.lastname: Reichlin
authors.forename: Y
authors.initials: Y
authors.lastname: Hu
authors.forename: B
authors.initials: B
authors.lastname: Canono
authors.forename: J C
authors.initials: JC
authors.lastname: Cambier
authors.forename: M C
authors.initials: MC
authors.lastname: Nussenzweig
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D020816:Amino Acid Motifs; D019943:Amino Acid Substitution; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology*; D001483:Base Sequence; D051925:CD79 Antigens; D003593:Cytoplasm / Q000378:metabolism*; D004247:DNA; D051379:Mice; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry; D010766:Phosphorylation; D011961:Receptors, Fc / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; D051925:CD79 Antigens; C497884:Cd79b protein, mouse; C045281:IgA receptor; D011961:Receptors, Fc; D014443:Tyrosine; D010649:Phenylalanine; D004247:DNA