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  • Oral presentation
  • Open Access

Preferential depletion of a splenic marginal zone-like peripheral blood CD27+B220- memory B cell population in HIV-1 infected individuals

  • 1,
  • 1,
  • 2,
  • 2 and
  • 1
Retrovirology20063 (Suppl 1) :S97

https://doi.org/10.1186/1742-4690-3-S1-S97

  • Published:

Keywords

  • Infected Individual
  • Marginal Zone
  • Humoral Immunity
  • Blood CD27
  • Cytidine Deaminase

In addition to CD4+ T cell depletion, HIV-1 infection is characterized by changes in humoral immunity including hypergammaglobulinemia, polyclonal B cell activation and loss of circulating memory B lymphocytes. Expression of the CD45 isoform B220 has recently been described on CD27- and a subset of CD27+ human B lymphocytes. The aim of this study was to evaluate B cell defects in HIV infection in more detail. We studied the frequency of memory B cells, based on the expression of B220, in HIV infected individuals (n = 27) and healthy controls (n = 22) and characterized their functional properties. RNA expression of TLR9 and activation-induced cytidine deaminase (AICD) was analyzed by Real-time PCR from B cells sorted according to their memory phenotype. In addition, B-cell proliferative responses and immunoglobulin secretion in response to SAC and ODN treatment were monitored.

We found that the previously described reduction in the frequency of CD27+ B cells in HIV-infected individuals affects preferentially the subset characterized by the lack of B220 expression. The proportion of CD27+B220- B cells expressing surface IgD (28.8%) and IgM (29.5%) was reduced in the HIV+ group compared to healthy controls (53.9% and 59.8%, respectively). This depletion did not correlate with either CD4 counts or viral load, and was not reversed by antiretroviral therapy. We found that CD27+B220- B cells have a splenic marginal zone like immunophenotype (IgMhiIgDloCD21+CD23-), express TLR9, and proliferate and secrete IgG and IgM in response to B cell specific ODN. In contrast, CD27+B220+ B cells are IgMloIgDhiCD21+CD23+, express AICD and proliferate in response to SAC but do not secrete immunoglobulins.

The lack of B220 expression on CD27+ B cells defines a distinct memory B cell compartment that is preferentially depleted in HIV-infected individuals. The phenotype, pattern of gene expression and functional properties of the preferentially depleted CD27+B220- B cells suggest that these cells are splenic marginal zone-like circulating memory B cells. The lack of these cells in HIV patients may play an important role in the defective immunity against T-independent pathogens and may impair the humoral control of HIV-1 propagation.

Authors’ Affiliations

(1)
Human Retrovirus Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, Maryland, USA
(2)
HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA

Copyright

© Morrow et al; licensee BioMed Central Ltd. 2006

This article is published under license to BioMed Central Ltd.

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