1. CD98hc facilitates B cell proliferation and adaptive humoral immunity.
- Author
-
Cantor, Joseph, Browne, Cecille D, Ruppert, Raphael, Féral, Chloé C, Fässler, Reinhard, Rickert, Robert C, and Ginsberg, Mark H
- Subjects
B-Lymphocytes ,Plasma Cells ,Cells ,Cultured ,Animals ,Mice ,Transgenic ,Mice ,Mitogen-Activated Protein Kinase 3 ,Integrins ,Lymphocyte Activation ,Cell Differentiation ,Cell Proliferation ,Antibody Formation ,Protein Binding ,Biological Transport ,Active ,Cyclin-Dependent Kinase Inhibitor p27 ,Fusion Regulatory Protein 1 ,Heavy Chain ,1.1 Normal biological development and functioning ,Immunology - 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.
- Published
- 2009