IgM memory B cells: a mouse/human paradox

Reynaud, Claude‐Agnès; Descatoire, Marc; Doğan, İsmail; Huetz, François; Weller, Sandra; Weill, Jean‐Claude

doi:10.1007/s00018-012-0971-z

Cited by 68 publications

(67 citation statements)

References 60 publications

(71 reference statements)

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“…2 and SI Appendix, Fig. S3), indirectly supporting prior hypotheses that distinct developmental pathways (possibly in response to different classes of antigen, adjuvant, and/or route of exposure) drive the development of these distinct B-cell subsets, as suggested previously (51)(52)(53).…”

Section: Discussionsupporting

confidence: 83%

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

DeKosky

Lungu

Park

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

185

191

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Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy-and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19− IgM-naive B cells, >120,000 antibody clusters from CD19+ antigenexperienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ-Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease.antibody | B cell | immunology | high-throughput sequencing | computational modeling E ffective antigen recognition by the humoral immune system is predicated on the somatic generation of a large antibody repertoire that encompasses the sequence and conformational diversity to respond to a highly diversified set of antigens (1-3). Upon antigen challenge, naive B cells (NBCs) expressing unmutated antibodies capable of binding antigen with an affinity sufficient to initiate B-cell receptor (BCR) signaling may be stimulated to undergo somatic hypermutation (SHM) of the antibody genes. B cells expressing higher-affinity BCRs are better equipped to compete for antigen and thus receive signals that enable their preferential proliferation and further antibody sequence diversification in additional rounds of SHM. This process generates a repertoire of somatically mutated antibodies that, at the structural level, generally display decreased conformational flexibility (4, 5), slower antigen dissociation rates, and increased binding selectivity relative to the germline repertoire.Understanding the salient features of the human antibody repertoire is critical for immunology research (6, 7). Specifically, additional information is needed regarding how a history of pathogen and environmental exposure modulates the sequence and conformational properties of naive antibodies to yield a mature antibody repertoire that confers effective protection. Hi...

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Section: Discussionsupporting

confidence: 83%

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

DeKosky

Lungu

Park

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

185

191

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“…Memory B lymphocytes display a considerable diversity, as reviewed by the groups of Reynaud and Weill176, 177 and Küppers,178 pointing also to differences between mice and humans. Memory B lymphocytes expressing switched isotypes of antibodies and IgM‐expressing memory B lymphocytes have been identified.…”

Section: Memory B Lymphocytes Of the Bone Marrowmentioning

confidence: 99%

Immunological memories of the bone marrow

Chang

Tokoyoda

Radbruch

2018

Immunological Reviews

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SummaryMemory for antigens once encountered is a hallmark of the immune system of vertebrates, providing us with an immunity adapted to pathogens of our environment. Despite its fundamental relevance, the cells and genes representing immunological memory are still poorly understood. Here we discuss the concept of a circulating, proliferating, and ubiquitous population of effector lymphocytes vs concepts of resting and dormant populations of dedicated memory lymphocytes, distinct from effector lymphocytes and residing in defined tissues, particularly in barrier tissues and in the bone marrow. The lifestyle of memory plasma cells of the bone marrow may serve as a paradigm, showing that persistence of memory lymphocytes is not defined by intrinsic “half‐lives”, but rather conditional on distinct survival signals provided by dedicated niches. These niches are organized by individual mesenchymal stromal cells. They define the capacity of immunological memory and regulate its homeostasis.

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“…Interestingly, we found significantly lower frequencies of IgM + memory B cells (means: 41.4 in the Lausanne cohort and 28.9 in the Entebbe cohort; P = 0.007) and higher frequencies of IgG + memory B cells (means: 28.5 in the Lausanne cohort and 39 in the Entebbe cohort; P = 0.004) in the Entebbe cohort when compared with the Lausanne cohort ( Figure 5C). Recent evidence suggests distinct functions between IgM + and IgG + memory B cells: IgM + memory B cells are believed to retain broader antibody specificities, have better survival ability, and, more importantly, can reinitiate germinal center formation during secondary responses (33,34). Thus, the high levels of IgM + memory B cells in the Lausanne cohort could provide more flexibility to the overall humoral immunity.…”

Section: Increased Baseline Activation Of the Adaptive Compartment Inmentioning

confidence: 99%

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

et al. 2014

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Background. Defining the parameters that modulate vaccine responses in African populations will be imperative to design effective vaccines for protection against HIV, malaria, tuberculosis, and dengue virus infections. This study aimed to evaluate the contribution of the patient-specific immune microenvironment to the response to the licensed yellow fever vaccine 17D (YF-17D) in an African cohort. Conclusion.Together, these results demonstrate that an activated immune microenvironment prior to vaccination impedes efficacy of the YF-17D vaccine in an African cohort and suggest that vaccine regimens may need to be boosted in African populations to achieve efficient immunity.Trial registration. Registration is not required for observational studies.

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IgM memory B cells: a mouse/human paradox

Cited by 68 publications

References 60 publications

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

Immunological memories of the bone marrow

Immune activation alters cellular and humoral responses to yellow fever 17D vaccine

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