Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells.

Sustained long-term antibody levels are the cornerstone of protective immunity, yet it remains unclear how they are durably maintained. A predominant theory implicates antigen-independent antibody production by a subset of long-lived plasma cells (LLPCs) that survive within bone marrow (BM). Central tenets of this model--that BM LLPCs constitute a subset defined by intrinsic biology distinct from PCs in other tissues and contribute to long-term antibody titers--have not been definitively demonstrated. We now report that long-term humoral immunity depends on the PC-intrinsic function of CD28, which selectively supports the survival of BM LLPC but not splenic short-lived PC (SLPC). LLPC and SLPC both express CD28, but CD28-driven enhanced survival occurred only in the LLPC. In vivo, even in the presence of sufficient T cell help, loss of CD28 or its ligands CD80 and CD86 caused significant loss of the LLPC population, reduction of LLPC half-life from 426 to 63 d, and inability to maintain long-term antibody titers, but there was no effect on SLPC populations. These findings establish the existence of the distinct BM LLPC subset necessary to sustain antibody titers and uncover a central role for CD28 function in the longevity of PCs and humoral immunity.

Citation

Cheryl H Rozanski, Ramon Arens, Louise M Carlson, Jayakumar Nair, Lawrence H Boise, Asher A Chanan-Khan, Stephen P Schoenberger, Kelvin P Lee. Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells. The Journal of experimental medicine. 2011 Jul 4;208(7):1435-46

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PMID: 21690252

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