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Clin Immunol. 2014 Aug;153(2):264-76. doi: 10.1016/j.clim.2014.04.017. Epub 2014 May 9.

Phenotypes and distribution of mucosal memory B-cell populations in the SIV/SHIV rhesus macaque model.

Author information

1
Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
2
Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD 20892, USA.
3
Section on Immune Biology of Retroviral Infection, Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA. Electronic address: guroffm@mail.nih.gov.

Abstract

As vaccine-elicited antibodies have now been associated with HIV protective efficacy, a thorough understanding of mucosal and systemic B-cell development and maturation is needed. We phenotyped mucosal memory B-cells, investigated isotype expression and homing patterns, and defined plasmablasts and plasma cells at three mucosal sites (duodenum, jejunum and rectum) in rhesus macaques, the commonly used animal model for pre-clinical vaccine studies. Unlike humans, macaque mucosal memory B-cells lacked CD27 expression; only two sub-populations were present: naïve (CD21(+)CD27(-)) and tissue-like (CD21(-)CD27(-)) memory. Similar to humans, IgA was the dominant isotype expressed. The homing markers CXCR4, CCR6, CCR9 and α4β7 were differentially expressed between naïve and tissue-like memory B-cells. Mucosal plasmablasts were identified as CD19(+)CD20(+/-)HLA-DR(+)Ki-67(+)IRF4(+)CD138(+/-) and mucosal plasma cells as CD19(+)CD20(-)HLA-DR(-)Ki-67(-)IRF4(+)CD138(+). Both populations were CD39(+/-)CD27(-). Plasma cell phenotype was confirmed by spontaneous IgA secretion by ELISpot of positively-selected cells and J-chain expression by real-time PCR. Duodenal, jejunal and rectal samples were similar in B-cell memory phenotype, isotype expression, homing receptors and plasmablast/plasma cell distribution among the three tissues. Thus rectal biopsies adequately monitor B-cell dynamics in the gut mucosa, and provide a critical view of mucosal B-cell events associated with development of vaccine-elicited protective immune responses and SIV/SHIV pathogenesis and disease control.

KEYWORDS:

Homing markers; Mucosal memory B cell phenotypes and distribution; Plasmablasts/plasma cells; SIV/SHIV rhesus macaque model

PMID:
24814239
PMCID:
PMC4086409
DOI:
10.1016/j.clim.2014.04.017
[Indexed for MEDLINE]
Free PMC Article

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