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

Cheryl H. Rozanski, Ramon Arens, Louise M. Carlson, Jayakumar Nair, Lawrence H. Boise, Asher A. Chanan-Khan, Stephen P. Schoenberger, Kelvin P. Lee

Research output: Contribution to journalArticle

107 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1435-1446
Number of pages12
JournalJournal of Experimental Medicine
Volume208
Issue number7
DOIs
StatePublished - Jul 4 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Rozanski, C. H., Arens, R., Carlson, L. M., Nair, J., Boise, L. H., Chanan-Khan, A. A., Schoenberger, S. P., & Lee, K. P. (2011). Sustained antibody responses depend on CD28 function in bone marrow-resident plasma cells. Journal of Experimental Medicine, 208(7), 1435-1446. https://doi.org/10.1084/jem.20110040