CD98hc facilitates B cell proliferation and adaptive humoral immunity.
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.
Cantor
Joseph
J
Department of Medicine, University of California San Diego, La Jolla, USA.
Browne
Cecille D
CD
Ruppert
Raphael
R
Féral
Chloé C
CC
Fässler
Reinhard
R
Rickert
Robert C
RC
Ginsberg
Mark H
MH
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
D027282:Fusion Regulatory Protein 1, Heavy Chain; D016023:Integrins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D048052:Mitogen-Activated Protein Kinase 3