Mucosal Plasma Cell Repertoire During HIV-1 Infection

Scamurra, Ronald W.; Nelson, Douglas B.; Lin, Xue; Miller, Darren J.; Silverman, Gregg J.; Kappel, Tim; Thurn, Joseph R.; Lorenz, Erin; Kulkarni-Narla, Anjali; Janoff, Edward N.

doi:10.4049/jimmunol.169.7.4008

Cited by 30 publications

(32 citation statements)

References 82 publications

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“…14 Furthermore, the significant loss of IgA, which is fundamental for humoral mucosal immunity, in all cmASCs measured may play a role in the chronic dysfunction of gastrointestinal tract immunity during HIV and SIV infection. This is also consistent with previous studies demonstrating a loss of IgA in HIV-infected individuals, 16,17 potentially an essential factor in the susceptibility to opportunistic infections arising in the mucosal immune system during HIV infection.…”

Section: Discussionsupporting

confidence: 82%

“…Thus, neo MML vaccination in the context of SIV infection results in decreased MML-specific cmASCs, specifically IgA-producing cmASCs, consistent with the finding that IgA levels are decreased in chronically HIV-infected individuals. 16,17 Recall MML vaccination responses also were altered in SIVinfected animals. Similar to neo vaccination responses, MMLspecific cmASC IgG responses also were slightly decreased in SIV-infected RMs (P ϭ .0952; Figure 5B left).…”

Section: Siv Infection Leads To Altered Mml-specific B-cell Functionamentioning

confidence: 86%

“…10 IgA may be of particular importance during HIV infection, because IgA plays a significant protective role at mucosal surfaces, 10 and given the common mucosal routes of HIV exposure. 15 Thus, the overall loss of IgA that is observed during HIV infection 16,17 may play a role in driving virus replication at mucosal sites as well as susceptibility to opportunistic infections. Furthermore, during chronic HIV infection, many other aspects of B-cell immunity are altered, including B-cell hyperactivation and increased B-cell turnover, increased production of autoantibodies, hypergammaglobulinaemia, and increased B cell-related malignancies.…”

Section: Introductionmentioning

confidence: 99%

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SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Klatt¹,

Vinton²,

Lynch

et al. 2011

Blood

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HIV infection is characterized by immune system dysregulation, including depletion of CD4 ؉ T cells, immune activation, and abnormal B-and T-cell responses. However, the immunologic mechanisms underlying lymphocytic dysfunctionality and whether it is restricted to immune responses against neo antigens, recall antigens, or both is unclear. Here, we immunized SIV-infected and uninfected rhesus macaques to induce immune responses against neo and recall antigens using a Leishmania major polyprotein (MML) vaccine given with poly-ICLC adjuvant. We found that vaccinated SIVuninfected animals induced high frequencies of polyfunctional MML-specific CD4 ؉ T cells. However, in SIV-infected animals, CD4 ؉ T-cell functionality decreased after both neo (P ‫؍‬ .0025) and recall (P ‫؍‬ . IntroductionHIV infection is characterized by progressive loss of CD4 ϩ T cells, eventually resulting in opportunistic infections and acquired immunodeficiency syndrome (AIDS) and, in untreated individuals, death. During acute HIV infection, CD4 ϩ T cells are massively infected and rapidly depleted from effector sites, particularly in mucosal tissues, and as infection progresses to chronic disease, there is a progressive, slow loss of peripheral CD4 ϩ T cells. [1][2][3][4][5][6][7] Furthermore, HIV specifically infects activated memory CD4 ϩ T cells, and previous studies have demonstrated that the virus preferentially infects CD4 ϩ T cells where the corresponding antigen is often present at high levels, such as HIV-specific and Mycobacterium tuberculosis-specific cells. 4,8 Hence, the immunodeficiency and dysfunctional immune responses that occur after HIV infection are of particular concern with respect to their role in providing immunity against opportunistic infections. The effectiveness of common vaccines in inducing healthy immune responses among chronically HIV-infected individuals against subsequent infection is decreased. 9 Indeed, the majority of currently effective vaccination approaches induce protective immunity against pathogens by induction of long-term antibody responses specific for the vaccinated antigen. 10 These antibodies are produced mainly by 2 subsets of B cells, plasma cells that reside primarily in the bone marrow and long-lived memory B cells. [11][12][13] Moreover, development of an effective B-cell response is reliant on helper CD4 ϩ T-cell responses that promote antigenspecific B-cell differentiation and antibody class switching. 14 Class switching by B cells from their constitutive expression and production of IgM to other antibody classes (ie, IgG and IgA) is essential to develop an effective immune response, because each type of immunoglobulin has specific functions and sites of activity. 10 IgA may be of particular importance during HIV infection, because IgA plays a significant protective role at mucosal surfaces, 10 and given the common mucosal routes of HIV exposure. 15 Thus, the overall loss of IgA that is observed during HIV infection 16,17 may play a role in driving virus replication at mucosal sites as we...

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Section: Discussionsupporting

confidence: 82%

Section: Siv Infection Leads To Altered Mml-specific B-cell Functionamentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Klatt¹,

Vinton²,

Lynch

et al. 2011

Blood

View full text Add to dashboard Cite

show abstract

“…While conventional antigens stimulate a small proportion of B cells, the proportion of B cells responsive to SAgs can be orders of magnitude higher. This unconventional mode of interaction with B cells, which is comparable to that of known SAgs with T lymphocytes [12], is being investigated for HIV-1 antigens, and a number of abnormalities and fluctuations of the B cell repertoire have been described [13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Down-modulation of the antigen receptor by a superantigen for human B cells

et al. 2004

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“…We are not aware of a previous analysis of V H family distribution in human ␣ 4 ␤ 7 ϩ memory B cells, but McCabe et al (11) analyzed V H usage in human intestinal B cells from colonoscopic biopsies and also found a VH4 dominance. In contrast, the V H gene repertoire in human intestinal plasma cells is VH3 dominated (12,13). Human Ab responses to capsular polysaccharides are encoded by the VH3 gene segment family (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

VH1–46 Is the Dominant Immunoglobulin Heavy Chain Gene Segment in Rotavirus-Specific Memory B Cells Expressing the Intestinal Homing Receptor α4β7

Weitkamp

Kallewaard

Bowen

et al. 2005

The Journal of Immunology

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Memory B cells expressing the intestinal homing marker α4β7 are important for protective immunity against human rotavirus (RV). It is not known whether the B cell repertoire of intestinal homing B cells differs from B cells of the systemic compartment. In this study, we analyzed the RV-specific VH and VL repertoire in human IgD− B cells expressing the intestinal homing marker α4β7. The mean frequency of RV-specific B cells in the systemic compartment of healthy adult subjects was 0.6% (range, 0.2–1.2). The mean frequency of IgD− B cells that were both RV specific and α4β7 was 0.04% (range, 0.01–0.1), and a mean of 10% (range, 1–32) of RV-specific peripheral blood human B cells exhibited an intestinal homing phenotype. We previously demonstrated that VH1–46 is the dominant Ab H chain gene segment in RV-specific systemic B cells from adults and infants. RV-specific systemic IgD− or intestinal homing IgD−/α4β7+ B cells in the current study also used the gene segment VH1–46 at a high frequency, while randomly selected B cells with those phenotypes did not. These data show that VH1–46 is the immunodominant gene segment in human RV-specific effector B cells in both the systemic compartment and in intestinal homing lymphocytes. The mean replacement/silent mutation ratio of systemic compartment IgD− B cells was >2, consistent with a memory phenotype and antigenic selection. Interestingly, RV-specific intestinal homing IgD−/α4β7+ B cells using the VH1–46 gene segment were not mutated, in contrast to systemic RV-specific IgD− B cells.

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Mucosal Plasma Cell Repertoire During HIV-1 Infection

Cited by 30 publications

References 82 publications

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

Down-modulation of the antigen receptor by a superantigen for human B cells

VH1–46 Is the Dominant Immunoglobulin Heavy Chain Gene Segment in Rotavirus-Specific Memory B Cells Expressing the Intestinal Homing Receptor α4β7

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