Inactivation of members of the nuclear factor-kappaB (NF-kappaB) family results in the decrease or defect of marginal zone B (MZB) cells. It is not known which inhibitors of the NF-kappaB family (IkappaB) are required for MZB cell development. Here, we show that mice with B cell-specific inactivation of the main NF-kappaB inhibitor IkappaBalpha have a marked decrease of MZB cells and their presumed precursors. They exhibited increased mortality rates after blood-borne bacterial infection, indicating the importance of MZB cells for bacterial clearance. In contrast, response to T cell-dependent and -independent antigens resulted only in minor changes in immunoglobulin production. Our data demonstrate the importance of the intact NF-kappaB/IkappaBalpha pathway for proper MZB cell development.
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