B cell signaling in context

Kwak, Kihyuck; Akkaya, Munir; Pierce, Susan K.

doi:10.1038/s41590-019-0427-9

Cited by 118 publications

(114 citation statements)

References 77 publications

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“…The Primary Interaction between BCRs and Antigens Generation of antibodies initiates with a weak electrostatic interaction between the membrane-bound BCR and the antigen [12][13][14]. The weak primary interaction may decay or, alternatively, evolve into a stronger secondary interaction that triggers an intracellular B-cell signaling cascade and a succession of events (namely, antigen internalization and presentation to helper T cells, VDJ recombination, somatic hypermutation, and class switch recombination) leading to the generation of high-affinity antibodies [15].…”

Section: Resultsmentioning

confidence: 99%

Hydrophobicity and the Physico-Chemical Basis of Immunotolerance

Kanduc

2020

Pathobiology

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Section: Resultsmentioning

confidence: 99%

Hydrophobicity and the Physico-Chemical Basis of Immunotolerance

Kanduc

2020

Pathobiology

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“…Within the GC, B cell survival and selection is dependent on antigen binding to the BCR and its downstream signalling pathways (Kwak et al, 2019). By using single-cell transcriptomics paired with BCR sequence analysis we have been able to uncouple antibody class, affinity and B cell phenotype at single-cell resolution.…”

Section: Discussionmentioning

confidence: 99%

“…During their maturation in germinal centres, B cells express their antibody immunoglobulin genes as part of a membrane-bound complex termed the B cell receptor (BCR). Antigen-binding and downstream signalling of the BCR is a primary determinant of GC B cell survival and even differentiation through differential expression of key transcription factors regulated by BCR-mediated signalling (Kwak et al, 2019, Shlomchik et al, 2019). Studies have shown that BCR activation thresholds and downstream signalling can differ as a result of isotype-specific differences in the extracellular, transmembrane and intracellular domains of immunoglobulin proteins forming the BCR (Martin and Goodnow, 2002, Engels et al, 2014, Xu et al, 2014b).…”

Section: Introductionmentioning

confidence: 99%

Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation

King

Orban

Riches

et al. 2020

Preprint

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15In response to antigen challenge, B cells clonally expand, undergo selection and differentiate to produce 16 mature B cell subsets and high affinity antibodies. However, the interplay between dynamic B cell states 17 and their antibody-based selection is challenging to decipher in primary human tissue. We have applied 18 an integrated analysis of bulk and single-cell antibody repertoires paired with single-cell transcriptomics 19 of human B cells undergoing affinity maturation. We define unique gene expression and antibody 20 repertoires of known and novel B cell states, including a pre-germinal centre state primed to undergo 21 class switch recombination. We dissect antibody class-dependent gene expression of germinal centre 22 and memory B cells to find that class switching prior to germinal centre entry dictates the capacity of B 23 cells to undergo antibody-based selection and differentiate. Together, our analyses provide 24 unprecedented resolution into the gene expression and selection dynamics that shape B cell-mediated 25 immunity. 26 27 121 122 157 sampling of IgH sequences from bulk repertoires to enhance genotype correction, identification of 158

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“…The activation of B cells and the subsequent downstream events that result in antibody production are consequences of the initial interaction between an antigen and the BCR. The signaling events initiated by this interaction, which are the subject of many excellent reviews [7][8][9], stimulate B cell proliferation and upregulate MHC Class II and the costimulatory molecules that permit subsequent interactions with T helper cells. B-cell activation is a quantitative phenomenon, in which the degree of activation is dependent on both the affinity of the BCR for its cognate antigen [10,11] and the valency of the antigen.…”

Section: The Molecular Events That Mediate B-cell Activation and The mentioning

confidence: 99%

Factors That Govern the Induction of Long-Lived Antibody Responses

Chackerian

Peabody

2020

Viruses

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The induction of long-lasting, high-titer antibody responses is critical to the efficacy of many vaccines. The ability to produce durable antibody responses is governed by the generation of the terminally differentiated antibody-secreting B cells known as long-lived plasma cells (LLPCs). Once induced, LLPCs likely persist for decades, providing long-term protection against infection. The factors that control the generation of this important class of B cells are beginning to emerge. In particular, antigens with highly dense, multivalent structures are especially effective. Here we describe some pathogens for which the induction of long-lived antibodies is particularly important, and discuss the basis for the extraordinary ability of multivalent antigens to drive differentiation of naïve B cells to LLPCs.

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B cell signaling in context

Cited by 118 publications

References 77 publications

Hydrophobicity and the Physico-Chemical Basis of Immunotolerance

Hydrophobicity and the Physico-Chemical Basis of Immunotolerance

Antibody repertoire and gene expression dynamics of diverse human B cell states during affinity maturation

Factors That Govern the Induction of Long-Lived Antibody Responses

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