CD98hc facilitates B cell proliferation and adaptive humoral immunity

Proliferation of antigen-specific lymphocytes and resulting clonal expansion is essential for adaptive immunity. We report that B cell-specific deletion of CD98hc reduced antibody responses due to total suppression of B cell proliferation and subsequent plasma cell formation. Deletion of CD98hc didn’t impair early B cell activation, but did inhibit later activation of the MAP kinase Erk1/2 and down regulation of the p27 cell cycle inhibitor. Reconstitution of CD98hc-deficient B cells with CD98hc mutants revealed that the integrin-binding domain of CD98hc is required, but the amino acid transport function of CD98hc is dispensable, for B cell proliferation. Thus, CD98hc supports integrin-dependent rapid proliferation of B cells. We propose that the advantage of adaptive immunity favored appearance of CD98hc in vertebrates.