title: CD98hc facilitates B cell proliferation and adaptive humoral immunity.
abstract: The proliferation of antigen-specific lymphocytes and resulting clonal expansion are essential for adaptive immunity. We report here that B cell-specific deletion of the heavy chain of CD98 (CD98hc) resulted in lower antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc did not impair early B cell activation but did inhibit later activation of the mitogen-activated protein kinase Erk1/2 and downregulation of the cell cycle inhibitor p27. Reconstitution of CD98hc-deficient B cells with CD98hc mutants showed that the integrin-binding domain of CD98hc was required for B cell proliferation but that the amino acid-transport function of CD98hc was dispensable for this. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored the appearance of CD98hc in vertebrates.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Cantor
authors.forename: Cecille D
authors.initials: CD
authors.lastname: Browne
authors.forename: Raphael
authors.initials: R
authors.lastname: Ruppert
authors.forename: Chloé C
authors.initials: CC
authors.lastname: Féral
authors.forename: Reinhard
authors.initials: R
authors.lastname: Fässler
authors.forename: Robert C
authors.initials: RC
authors.lastname: Rickert
authors.forename: Mark H
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001693:Biological Transport, Active; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D027282:Fusion Regulatory Protein 1, Heavy Chain / Q000276:immunology*; D016023:Integrins / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology; D011485:Protein Binding
chemical_list: D027282:Fusion Regulatory Protein 1, Heavy Chain; D016023:Integrins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048052:Mitogen-Activated Protein Kinase 3