IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells

Immunization with a T cell–dependent antigen elicits production of specific memory B cells and antibody-secreting cells (ASCs). The kinetic and developmental relationships between these populations and the phenotypic forms they and their precursors may take remain unclear. Therefore, we examined the early stages of a primary immune response, focusing on the appearance of antigen-specific B cells in blood. Within 1 wk, antigen-specific B cells appear in the blood with either a memory phenotype or as immunoglobulin (Ig)G1 ASCs expressing blimp-1. The memory cells have mutated VH genes; respond to the chemokine CXCL13 but not CXCL12, suggesting recirculation to secondary lymphoid organs; uniformly express B220; show limited differentiation potential unless stimulated by antigen; and develop independently of blimp-1 expression. The antigen-specific IgG1 ASCs in blood show affinity maturation paralleling that of bone marrow ASCs, raising the possibility that this compartment is established directly by blood-borne ASCs. We find no evidence for a blimp-1–expressing preplasma memory compartment, suggesting germinal center output is restricted to ASCs and B220+ memory B cells, and this is sufficient to account for the process of affinity maturation.

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Faculty Opinions recommendation of Timing of HAART defines the integrity of memory B cells and the longevity of humoral responses in HIV-1 vertically-infected children.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1159342.619689 ◽

2009 ◽

Author(s):

Matthew Dolan

Keyword(s):

B Cells ◽

Memory B Cells ◽

Humoral Responses ◽

Hiv 1

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Faculty Opinions recommendation of Analysis of dengue specific memory B cells, neutralizing antibodies and binding antibodies in healthy adults from India.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.734880811.793581248 ◽

2020 ◽

Author(s):

Tian Wang

Keyword(s):

B Cells ◽

Neutralizing Antibodies ◽

Memory B Cells ◽

Healthy Adults ◽

Specific Memory

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Limiting dilution analysis of virus-specific memory B cells by an ELISPOT assay

Journal of Immunological Methods ◽

10.1016/s0022-1759(96)00146-9 ◽

1996 ◽

Vol 199 (1) ◽

pp. 37-46 ◽

Cited By ~ 75

Author(s):

Mark K. Slifka ◽

Rafi Ahmed

Keyword(s):

B Cells ◽

Elispot Assay ◽

Memory B Cells ◽

Limiting Dilution Analysis ◽

Specific Memory ◽

Limiting Dilution

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An optimized assay for the enumeration of antigen-specific memory B cells in different compartments of the human body

Journal of Immunological Methods ◽

10.1016/j.jim.2010.03.009 ◽

2010 ◽

Vol 358 (1-2) ◽

pp. 56-65 ◽

Cited By ~ 31

Author(s):

Yanran Cao ◽

Maja Gordic ◽

Sebastian Kobold ◽

Nesrine Lajmi ◽

Sabrina Meyer ◽

...

Keyword(s):

B Cells ◽

Human Body ◽

Memory B Cells ◽

Specific Memory

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Induction of long-lived germinal centers associated with persisting antigen after viral infection.

Journal of Experimental Medicine ◽

10.1084/jem.183.5.2259 ◽

1996 ◽

Vol 183 (5) ◽

pp. 2259-2269 ◽

Cited By ~ 132

Author(s):

M F Bachmann ◽

B Odermatt ◽

H Hengartner ◽

R M Zinkernagel

Keyword(s):

T Cell ◽

B Cells ◽

Viral Infection ◽

Neutralizing Antibody ◽

Germinal Centers ◽

Memory B Cells ◽

Specific Memory ◽

Specific Amplification ◽

Antibody Levels ◽

Red Pulp

Vesicular stomatitis virus (VSV) induces an early T cell-independent neutralizing lgM response that is followed by a long-lived, T cell-dependent lgG response. We used the specific amplification factor of several 100x of VSV-virions for immunohistology to analyze the localization of VSV-specific B cells at different time points after immunization. At the peak of the IgM response (day 4), VSV-specific B cells were predominantly present in the red pulp and marginal zone but not in the T area. These B cells were mostly stained in the cytoplasm, characterizing them as antibody secreting cells. By day 6 after immunization, germinal centers (GC) containing surface-stained VSV-specific B cells became detectable and were fully established by day 12. At the same time, large VSV-specific B cell aggregates were present in the red pulp. High numbers of VSV-specific GC associated with persisting antigen were present 1 mo after immunization and later, i.e., considerably longer than has been observed for haptens. Some GC, exhibiting follicular dendritic cells and containing VSV-specific, proliferating B cells were still detectable up to 100 d after immunization. Long-lived GC were also observed after immunization with recombinant VSV-glycoprotein in absence of adjuvants. Thus some anti-virally protective (memory) B cells are cycling and locally proliferate in long-lived GC in association with persisting antigen and therefore seem responsible for long-term maintenance of elevated antibody levels. These observations extend earlier studies with carrier hapten antigens in adjuvant depots or complexed with specific IgG; they are the first to show colocalization of antigen and specific memory B cells and to analyze a protective neutralizing antibody response against an acute viral infection.

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COVID-19 convalescents exhibit deficient humoral and T cell responses to variant of concern Spike antigens at 12 month post-infection

10.1101/2021.11.08.21266035 ◽

2021 ◽

Author(s):

Pablo Garcia-Valtanen ◽

Christopher Martin Hope ◽

Makutiro Ghislain Masavuli ◽

Arthur Eng Lip Yeow ◽

Harikrishnan Balachandran ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

B Cells ◽

Post Infection ◽

T Cell Responses ◽

Memory B Cells ◽

Pseudotyped Virus ◽

Cell Responses ◽

Specific Memory ◽

Cell Functionality

Background The duration and magnitude of SARS-CoV-2 immunity after infection, especially with regard to the emergence of new variants of concern (VoC), remains unclear. Here, immune memory to primary infection and immunity to VoC was assessed in mild-COVID-19 convalescents one year after infection and in the absence of viral re-exposure or COVID-19 vaccination. Methods Serum and PBMC were collected from mild-COVID-19 convalescents at ~6 and 12 months after a COVID-19 positive PCR (n=43) and from healthy SARS-CoV-2-seronegative controls (n=15-40). Serum titers of RBD and Spike-specific Ig were quantified by ELISA. Virus neutralisation was assessed against homologous, pseudotyped virus and homologous and VoC live viruses. Frequencies of Spike and RBD-specific memory B cells were quantified by flow cytometry. Magnitude of memory T cell responses was quantified and phenotyped by activation-induced marker assay, while T cell functionality was assessed by intracellular cytokine staining using peptides specific to homologous Spike virus antigen and four VoC Spike antigens. Findings At 12 months after mild-COVID-19, >90% of convalescents remained seropositive for RBD-IgG and 88.9% had circulating RBD-specific memory B cells. Despite this, only 51.2% convalescents had serum neutralising activity against homologous live-SARS-CoV-2 virus, which decreased to 44.2% when tested against live B.1.1.7, 4.6% against B.1.351, 11.6% against P.1 and 16.2%, against B.1.617.2 VoC. Spike and non-Spike-specific T cells were detected in >50% of convalescents with frequency values higher for Spike antigen (95% CI, 0.29-0.68% in CD4+ and 0.11-0.35% in CD8+ T cells), compared to non-Spike antigens. Despite the high prevalence and maintenance of Spike-specific T cells in Spike 'high-responder' convalescents at 12 months, T cell functionality, measured by cytokine expression after stimulation with Spike epitopes corresponding to VoC was severely affected. Interpretations SARS-CoV-2 immunity is retained in a significant proportion of mild COVID-19 convalescents 12 months post-infection in the absence of re-exposure to the virus. Despite this, changes in the amino acid sequence of the Spike antigen that are present in current VoC result in virus evasion of neutralising antibodies, as well as evasion of functional T cell responses.

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Antigen-Specific B Cell Memory

Journal of Experimental Medicine ◽

10.1084/jem.191.7.1149 ◽

2000 ◽

Vol 191 (7) ◽

pp. 1149-1166 ◽

Cited By ~ 135

Author(s):

Louise J. McHeyzer-Williams ◽

Melinda Cool ◽

Michael G. McHeyzer-Williams

Keyword(s):

Bone Marrow ◽

B Cells ◽

B Cell ◽

Memory B Cells ◽

Cell Memory ◽

Specific Memory ◽

B Cell Memory ◽

Cellular Components

The mechanisms that regulate B cell memory and the rapid recall response to antigen remain poorly defined. This study focuses on the rapid expression of B cell memory upon antigen recall in vivo, and the replenishment of quiescent B cell memory that follows. Based on expression of CD138 and B220, we reveal a unique and major subtype of antigen-specific memory B cells (B220−CD138−) that are distinct from antibody-secreting B cells (B220+/−CD138+) and B220+CD138− memory B cells. These nonsecreting somatically mutated B220− memory responders rapidly dominate the splenic response and comprise >95% of antigen-specific memory B cells that migrate to the bone marrow. By day 42 after recall, the predominant quiescent memory B cell population in the spleen (75–85%) and the bone marrow (>95%) expresses the B220− phenotype. Upon adoptive transfer, B220− memory B cells proliferate to a lesser degree but produce greater amounts of antibody than their B220+ counterparts. The pattern of cellular differentiation after transfer indicates that B220− memory B cells act as stable self-replenishing intermediates that arise from B220+ memory B cells and produce antibody-secreting cells on rechallenge with antigen. Cell surface phenotype and Ig isotype expression divide the B220− compartment into two main subsets with distinct patterns of integrin and coreceptor expression. Thus, we identify new cellular components of B cell memory and propose a model for long-term protective immunity that is regulated by a complex balance of committed memory B cells with subspecialized immune function.

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