Tissue memory B cell repertoire analysis after ALVAC/AIDSVAX B/E gp120 immunization of rhesus macaques

ABSTRACTMemory B cell reserves can generate protective antibodies against repeated SARS-CoV-2 infections, but with an unknown reach from original infection to antigenically drifted variants. We charted memory B cell receptor-encoded monoclonal antibodies (mAbs) from 19 COVID-19 convalescent subjects against SARS-CoV-2 spike (S) and found 7 major mAb competition groups against epitopes recurrently targeted across individuals. Inclusion of published and newly determined structures of mAb-S complexes identified corresponding epitopic regions. Group assignment correlated with cross-CoV-reactivity breadth, neutralization potency, and convergent antibody signatures. mAbs that competed for binding the original S isolate bound differentially to S variants, suggesting the protective importance of otherwise-redundant recognition. The results furnish a global atlas of the S-specific memory B cell repertoire and illustrate properties conferring robustness against emerging SARS-CoV-2 variants.

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Functional Enrichment and Analysis of Antigen-Specific Memory B Cell Antibody Repertoires in PBMCs

10.1101/557769 ◽

2019 ◽

Cited By ~ 1

Author(s):

Eric Waltari ◽

Aaron McGeever ◽

Peter S. Kim ◽

Krista M. McCutcheon

Keyword(s):

B Cell ◽

Plasma Cells ◽

Functional Enrichment ◽

Cell Repertoire ◽

Culture Methods ◽

Memory B Cell ◽

Low Frequencies ◽

Specific Memory ◽

B Cell Repertoire ◽

And Function

Phenotypic screening of antigen-specific antibodies in human blood is a common diagnostic test for infectious agents and a correlate of protection after vaccination. In addition to long-lived antibody secreting plasma cells residing in the bone marrow, memory B cells are a latent source of antigen-experienced, long-term immunity that can be found at low frequencies in circulating PBMCs. Assessing the genotype, clonal frequency, quality, and function of antibodies resulting from an individual’s persistent memory B cell repertoire can help inform the success or failure of immune protection. We have applied ELISPOT cell culture methods to functionally expand the memory repertoire from PBMCs and clonally map monoclonal antibodies from this population. We show that combining deep sequencing of stimulated memory B cell repertoires with retrieving single antigen-specific cells is a promising approach in evaluating the latent, functional B cell memory in PBMCs.

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Review for "Templated Insertions at VD and DJ junctions Create Unique B‐Cell Receptors in the Healthy B‐Cell Repertoire"

10.1002/eji.202048828/v1/review2 ◽

2018 ◽

Keyword(s):

B Cell ◽

B Cell Receptors ◽

Cell Repertoire ◽

Cell Receptors ◽

B Cell Repertoire

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Selection of the expressed B cell repertoire by infusion of normal immunoglobulin G in a patient with autoimmune thyroiditis

European Journal of Immunology ◽

10.1002/eji.1830231133 ◽

1993 ◽

Vol 23 (11) ◽

pp. 2945-2950 ◽

Cited By ~ 40

Author(s):

Gilles Dietrich ◽

Francisco J. Varela ◽

Vincent Hurez ◽

Majida Bouanani ◽

Michel D. Kazatchkine

Keyword(s):

B Cell ◽

Immunoglobulin G ◽

Autoimmune Thyroiditis ◽

Cell Repertoire ◽

B Cell Repertoire ◽

Selection Of

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Monoclonal CD5+ and CD5- B-lymphocyte expansions are frequent in the peripheral blood of the elderly

Blood ◽

10.1182/blood-2003-09-3277 ◽

2004 ◽

Vol 103 (6) ◽

pp. 2337-2342 ◽

Cited By ~ 164

Author(s):

Paolo Ghia ◽

Giuseppina Prato ◽

Cristina Scielzo ◽

Stefania Stella ◽

Massimo Geuna ◽

...

Keyword(s):

B Cell ◽

Peripheral Blood ◽

B Lymphocyte ◽

The Elderly ◽

Lymphocytic Leukemia ◽

Pcr Analysis ◽

Cell Repertoire ◽

Healthy Elderly ◽

B Cell Repertoire ◽

Igh Genes

Abstract The responsiveness and diversity of peripheral B-cell repertoire decreases with age, possibly because of B-cell clonal expansions, as suggested by the incidence of serum monoclonal immunoglobulins and of monoclonal chronic lymphocytic leukemia (CLL)–like B lymphocytes in clinically silent adults. We phenotyped peripheral blood cells from 500 healthy subjects older than 65 years with no history or suspicion of malignancies and no evidence of lymphocytosis. In 19 cases (3.8%) a κ/λ ratio of more than 3:1 or less than 1:3 was found: 9 were CD5+, CD19+, CD23+, CD20low, CD79blow, sIglow (classic CLL-like phenotype); 3 were CD5+, CD19+, CD23+, CD20high, CD79blow, sIglow (atypical CLL-like), and 7 were CD5-, CD19+, CD20high, CD23-, CD79bbright, FMC7+, sIgbright (non–CLL-like). In 2 subjects, 2 phenotypically distinct unrelated clones were concomitantly evident. No cases were CD10+. Polymerase chain reaction (PCR) analysis demonstrated a monoclonal rearrangement of IgH genes in 15 of 19 cases. No bcl-1 or bcl-2 rearrangements were detected. Using a gating strategy based on CD20/CD5/CD79 expression, 13 additional CLL-like B-cell clones were identified (cumulative frequency of classic CLL-like: 5.5%). Thus, phenotypically heterogeneous monoclonal B-lymphocyte expansions are common among healthy elderly individuals and are not limited to classic CLL-like clones but may have the phenotypic features of different chronic lymphoproliferative disorders, involving also CD5- B cells.

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