Abstract
BackgroundSeveral B-cell defects arise in HIV infected patients, particularly in patients with chronic infection and high viral load. Loss of memory B cells (CD27+ B cells) in peripheral blood and lymphoid tissues is one of the major B cell dysfunctions in HIV and simian immunodeficiency virus (SIV) infection. Despite several studies, definitive identification of memory B cells based on CD27 surface expression has not been described. Similarly, the rates of cell turnover in different B cell subpopulation from lymphoid and mucosal tissues have not been well documented. In this study, we demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues.Methodology/Principal FindingsThirteen healthy, uninfected rhesus macaques were selected for this study. CD20+ B cells were isolated from peripheral blood and sorted based on CD27 and CD21 surface markers to define memory B cell population. All the B cell subpopulation was further characterized phenotypically and their cell turnover rates were evaluated in vivo following bromodeoxyuridine (BrdU) inoculation. Double positive (DP) CD21+CD27+ B cells in both peripheral and lymphoid tissues are memory B cells, able to produce antibody by polyclonal activation, and without T cell help. Peripheral and lymphoid DP CD21+CD27+ B cells were also able to become activated and proliferate at higher rates than other B cell subpopulations. Increased turnover of tonsillar memory B cells were identified compared to other tissues examined.Conclusions/SignificanceWe suggest that this DP memory B cells play a major role in the immune system and their function and proliferation might have an important role in HIV/SIV mediated B cell dysregulation and pathogenesis.
Highlights
Immunological memory is a crucial feature of adaptive immunity, whereby the first encounter with a pathogen is imprinted indelibly into the immune system [1]
CD21 expression differs between peripheral blood and lymphoid tissue B cells In order to determine the distribution of CD21 surface marker in relation to CD27 expression, we performed extensive analysis of B cells from PB and different lymphoid tissues in normal rhesus macaques (RMs)
The frequencies of single positive (SP) CD27+, SP CD21+, Double positive (DP) CD21+CD27+ and double negative CD272CD212 B cells were determined in PB, axillary lymph node (ALN), bone marrow (BM), bronchoalveolar lavage (BAL), spleen, tonsil and jejunum lamina propria lymphocytes (LPL) of 13 normal RMs by flow cytometry (Fig. 1A & B)
Summary
Immunological memory is a crucial feature of adaptive immunity, whereby the first encounter with a pathogen is imprinted indelibly into the immune system [1]. After exposure to a T cell-dependent antigen, naıve B cells can differentiate either rapidly differentiating shortlived immunoglobulin secreting cells or long-lived plasma cells or memory B cells [4,5,6,7] These newly generated memory B cells can re-enter the circulation or remain as resident cells within discrete regions of secondary lymphoid tissue, like marginal zone of spleen or mucosal epithelium of tonsil [5,8,9,10,11]. We demonstrate the presence of memory B cell populations and define their distribution, frequency and immunophenotype with regards to activation, proliferation, maturation, and antibody production in normal rhesus macaques from different lymphoid tissues
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