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Address correspondence to Katia Georgopoulos, Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Building 149, 13th Street, 3rd Floor, Charlestown, MA 02129. Phone: (617) 726-4445; Fax: (617) 726-4453; email: katia.georgopoulos{at}cbrc2.mgh.harvard.edu
Antigenic encounter generates long-term immunity sustained by long-lived high affinity plasma cells resident in the bone marrow (BM). Here we show that the Ikaros family member, Aiolos, is specifically required for the generation of these plasma cells. Failure to generate high affinity plasma cells in the BM and to sustain serum antibody titers is apparent after both primary and secondary immunization of Aiolos-/- mice with a range of hapten concentrations. Chimera reconstitutions demonstrate that the BM plasma cell defect is B cell intrinsic. Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation. No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge. These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos.
Key Words: plasma cell subsets • long-term antibody production • immunologic memory • Aiolos • transcription factor
globulin; GC, germinal center; NP, nitrophenyl; R/S, ratio of amino acid replacement to silent mutations.
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