Evaluation of B Cell Function in Patients with HIV

Buckner, Clarisa M.; Kardava, Lela; Moir, Susan

doi:10.1002/0471142735.im1213s100

Cited by 7 publications

(9 citation statements)

References 16 publications

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“…Frequencies of PBs and PCs secreting IgG, IgA and IgM, as well as those specific for gp140, were measured by ELISPOT, as previously described (24). Briefly, Immobilon-P polyvinylidene difluoride membrane plates (MAIPSWU10; Millipore) were coated with 5 μg/ml anti-Ig light-chain antibodies (Rockland Immunochemicals), followed by addition of sorted plasma cells, incubation overnight, and detection with biotinylated antibodies against each of the Ig classes or biotinylated YU2-gp140-F. Unlabeled or biotinyated Keyhole limpet hemocyanin served as negative control antigen.…”

Section: Methodsmentioning

confidence: 99%

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Montezuma-Rusca

Moir

Kardava

et al. 2015

The Journal of Immunology

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Several potent and broadly neutralizing antibodies to HIV-1 have been isolated recently from peripheral blood B cells of infected individuals, based on pre-screening of antibody activity in the serum. However, little is known regarding the cells that make the antibodies that circulate in the blood. Accordingly, we investigated the most likely source, the bone marrow, of chronically HIV-1-infected individuals who were not receiving antiretroviral therapy. Increased frequencies of plasma cells, as well as B cell precursors, namely preB-I, preB-II, and decreased frequencies of mature B cells were observed in bone marrow aspirates of these individuals compared to HIV-negative counterparts. Increased frequencies of bone marrow plasma cells are consistent with known hallmarks of HIV-1 infection, namely hypergammaglobulinemia and increased frequencies of peripheral blood plasmablasts. Levels of HIV-1 envelope (Env)-binding and HIV-1-neutralizing antibodies were measured in serum and corresponding frequencies of antibody-secreting or Env-binding cells were measured in the blood (plasmablasts and memory B cells) and in the bone marrow (plasma cells). A strong correlation was observed between serum HIV-1-specific antibodies and Env-specific bone marrow-derived plasma cells, but not circulating plasmablasts or memory B cells. These findings demonstrate that despite HIV-1-induced phenotypic and functional B-cell dysregulation in the peripheral blood and secondary lymphoid tissues, bone marrow plasma cells remain a primary source for circulating HIV-1-specific antibodies in HIV-1-infected individuals.

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Section: Methodsmentioning

confidence: 99%

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Montezuma-Rusca

Moir

Kardava

et al. 2015

The Journal of Immunology

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“…These B cells can be clearly identified by the expression of high levels of CD27 and reduced levels of CD20 and CD21, as well as very high levels of CD38 (18). Finally, whereas tissue-derived plasma cells can be negative for CD19 (45), plasmablasts express CD19, albeit at reduced levels compared with other B cells, a feature that when combined with a higher side scatter in phenotypic analyses can be used to easily identify plasmablasts among a preparation of B cells or PBMCs (46). In this regard, the majority of terminally differentiated B cells that circulate in the blood in both HIV disease and other conditions are likely to be plasmablasts, because the majority express the cell-cycling marker Ki-67 and the pan B-cell marker CD19 and are negative for CD138, the most widely expressed marker on tissue-derived plasma cells (43,44).…”

Section: Alterations In Terminally Differentiating B Cellsmentioning

confidence: 99%

“…In this regard, the majority of terminally differentiated B cells that circulate in the blood in both HIV disease and other conditions are likely to be plasmablasts, because the majority express the cell-cycling marker Ki-67 and the pan B-cell marker CD19 and are negative for CD138, the most widely expressed marker on tissue-derived plasma cells (43,44). Finally, whereas tissue-derived plasma cells can be negative for CD19 (45), plasmablasts express CD19, albeit at reduced levels compared with other B cells, a feature that when combined with a higher side scatter in phenotypic analyses can be used to easily identify plasmablasts among a preparation of B cells or PBMCs (46).…”

Section: Alterations In Terminally Differentiating B Cellsmentioning

confidence: 99%

Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals

Moir

Fauci

2013

Immunological Reviews

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Human immunodeficiency virus (HIV) disease is associated with dysregulation and dysfunction involving all major lymphocyte populations, including B cells. Such perturbations occur early in the course of infection and are driven in large part by immune activation resulting from ongoing HIV replication leading to bystander effects on B cells. While most of the knowledge regarding immune cell abnormalities in HIV-infected individuals has been gained from studies conducted on the peripheral blood, it is clear that the virus is most active and most damaging in lymphoid tissues. Here, we discuss B-cell perturbations in HIV-infected individuals, focusing on the skewing of B-cell subsets that circulate in the peripheral blood and their counterparts that reside in lymphoid tissues. This review also highlights recent advances in evaluating HIV-specific B-cell responses both in the memory B-cell compartment, as well as in circulating antibody-secreting plasmablasts and the more differentiated plasma cells residing in tissues. Finally, we consider how knowledge gained by investigating B cells in HIV-infected individuals may help inform the development of an effective antibody-based HIV vaccine.

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“…Hypergammaglobulinemia, polyclonal activation, poor immune responses to pathogens and vaccine antigens, imbalance in B cell subsets, and increased B cell turnover have been associated with persistent HIV/SIV replication and represent important features of B cell dysfunction (40). Numerous studies carried out with both humans and rhesus macaques (RMs) suggested that this B cell dysfunction may play a central role in the progression to AIDS (41), through alterations of the different subsets of circulating or tissue-resident B cells (42) and low antibody (Ab) responses (43,44). A generalized loss of memory B cells was reported to be the major characteristic of B cell dysfunction in SIV-infected RMs (45).…”

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confidence: 99%

Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction

Brocca-Cofano

Kuhrt

Siewe

et al. 2017

J Virol

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We compared and contrasted pathogenic (in pig-tailed macaques [PTMs]) and nonpathogenic (in African green monkeys [AGMs]) SIVsab infections to assess the significance of the B cell dysfunction observed in simian (SIV) and human immunodeficiency virus (HIV) infections. We report that the loss of B cells is specifically associated with the pathogenic SIV infection, while in the natural hosts, in which SIV is nonpathogenic, B cells rapidly increase in both lymph nodes (LNs) and intestine. SIV-associated B cell dysfunction associated with the pathogenic SIV infection is characterized by loss of naive B cells, loss of resting memory B cells due to their redistribution to the gut, increases of the activated B cells and circulating tissue-like memory B cells, and expansion of the B regulatory cells (Bregs). While circulating B cells are virtually restored to preinfection levels during the chronic pathogenic SIV infection, restoration is mainly due to an expansion of the "exhausted," virus-specific B cells, i.e., activated memory cells and tissue-like memory B cells. Despite of the B cell dysfunction, SIV-specific antibody (Ab) production was higher in the PTMs than in AGMs, with the caveat that rapid disease progression in PTMs was strongly associated with lack of anti-SIV Ab. Neutralization titers and the avidity and maturation of immune responses did not differ between pathogenic and nonpathogenic infections, with the exception of the conformational epitope recognition, which evolved from low to high conformations in the natural host. The patterns of humoral immune responses in the natural host are therefore more similar to those observed in HIV-infected subjects, suggesting that natural hosts may be more appropriate for modeling the immunization strategies aimed at preventing HIV disease progression. The numerous differences between the pathogenic and nonpathogenic infections with regard to dynamics of the memory B cell subsets point to their role in the pathogenesis of HIV/SIV infections and suggest that monitoring B cells may be a reliable approach for assessing disease progression. We report here that the HIV/SIV-associated B cell dysfunction (defined by loss of total and memory B cells, increased B regulatory cell [Breg] counts, and B cell activation and apoptosis) is specifically associated with pathogenic SIV infection and absent during the course of nonpathogenic SIV infection in natural nonhuman primate hosts. Alterations of the B cell population are not correlated with production of neutralizing antibodies, the levels of which are similar in the two species. Rapid progressive infections are associated with a severe impairment in SIV-specific antibody production. While we did not find major differences in avidity and maturation between the pathogenic and nonpathogenic SIV infections, we identified a major difference in conformational epitope recognition, with the nonpathogenic infection being characterized by an evolution from low to high conformations. B cell dysfunction should be considered in designing imm...

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Evaluation of B Cell Function in Patients with HIV

Cited by 7 publications

References 16 publications

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Bone Marrow Plasma Cells Are a Primary Source of Serum HIV-1–Specific Antibodies in Chronically Infected Individuals

Insights into B cells and HIV‐specific B‐cell responses in HIV‐infected individuals

Pathogenic Correlates of Simian Immunodeficiency Virus-Associated B Cell Dysfunction

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