The unique biology of germinal center B cells

Young, Clara; Brink, Robert

doi:10.1016/j.immuni.2021.07.015

Cited by 127 publications

(101 citation statements)

References 135 publications

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“…Given that it takes years for bnAbs to emerge during infection ( 61 ), generation of rare high quality bnAb-producing clones may require prolonged GC responses, which may simply reflect the need for many rounds of SHM ( 3 ). Alternatively, it is also possible that prolonged GCs include more clonally permissive B cells over time.…”

Section: Generation Of Broadly-neutralizing Memory B Cells and Their Recallmentioning

confidence: 99%

“…Humoral immunological memory, the basis of antibody (Ab)-based vaccination, is critical for protection against pathogen re-infection, which is largely mediated by two cellular compartments, long-lived plasma cells and memory B cells. Early memory B cells emerge after the initial immunization are primarily composed of IgM-expressing B cells harboring a small number of somatic hypermutation (SHM), whereas subsequent memory B cell development occurs in the germinal center (GC), the primary site in which iterative rounds of SHM and subsequent selection of affinity-matured B cell clones take place (1)(2)(3).…”

Section: Introductionmentioning

confidence: 99%

“…Although we briefly touch upon pre-GC processes, more thorough reviews of these topics are available elsewhere ( 11 , 12 ). Likewise, differentiation of GC B cells to plasma cells has been extensively reviewed in recent years ( 3 , 13 ) and is beyond the scope of this article.…”

Section: Introductionmentioning

confidence: 99%

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Generation of High Quality Memory B Cells

2022

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Protection against pathogen re-infection is mediated, in large part, by two humoral cellular compartments, namely, long-lived plasma cells and memory B cells. Recent data have reinforced the importance of memory B cells, particularly in response to re-infection of different viral subtypes or in response with viral escape mutants. In regard to memory B cell generation, considerable advancements have been made in recent years in elucidating its basic mechanism, which seems to well explain why the memory B cells pool can deal with variant viruses. Despite such progress, efforts to develop vaccines that induce broadly protective memory B cells to fight against rapidly mutating pathogens such as influenza virus and HIV have not yet been successful. Here, we discuss recent advances regarding the key signals and factors regulating germinal center-derived memory B cell development and activation and highlight the challenges for successful vaccine development.

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Section: Generation Of Broadly-neutralizing Memory B Cells and Their Recallmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Generation of High Quality Memory B Cells

2022

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“…42,43 The conditions under which memory T cells differentiate are not only influenced by the host immune environment and the antigen (sustained low T cell receptor signals, co-stimulation, and cytokines) 43,44 The differentiation of memory B cells also results from many factors, among which class-switch recombination (CSR) and somatic hypermutation (SHM) play a decisive role in the differentiation bias towards plasma and memory B cells. 45,46 The presence of memory B and T immune cells is crucial for the permanent preventative or curative effects against a disease. 47 Induction of an efficacious specific immune response and maintenance of long-term immune memory with low doses of antigen are primary avenues of current vaccine research.…”

Section: The Adaptive Immune Systemmentioning

confidence: 99%

Engineering optimal vaccination strategies: effects of physical properties of the delivery system on functions

2022

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“…The GC has been traditionally divided into two histological and functionally distinct compartments: the dark zone (DZ), representing the site where cells proliferate and immunoglobulin somatic hypermutation (SHM) occurs, and the light zone (LZ), where affinity-based selection takes place (2)(3)(4). More recent insights in GC biology, mostly based on single cell (sc)-RNAseq analyses of mouse and human cells, clearly showed that the GC reaction is better explained by a continuum of cell states between the DZ and the LZ (5,6). Indeed, about one third of GC B cells display a transcriptomic and phenotypic profile that is intermediate between DZ and LZ features (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Tracking Immunoglobulin Repertoire and Transcriptomic Changes in Germinal Center B Cells by Single-Cell Analysis

et al. 2022

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In response to T-cell-dependent antigens, mature B cells in the secondary lymphoid organs are stimulated to form germinal centers (GCs), which are histological structures deputed to antibody affinity maturation, a process associated with immunoglobulin gene editing by somatic hypermutation (SHM) and class switch recombination (CSR). GC B cells are heterogeneous and transition across multiple stages before being eliminated by apoptosis or committing to post-GC differentiation as memory B cells or plasma cells. In order to explore the dynamics of SHM and CSR during the GC reaction, we identified GC subpopulations by single-cell (sc) transcriptomics and analyzed the load of immunoglobulin variable (V) region mutations as well as the isotype class distribution in each subpopulation. The results showed that the large majority of GC B cells display a quantitatively similar mutational load in the V regions and analogous IGH isotype class distribution, except for the precursors of memory B cells (PreM) and plasma cells (PBL). PreM showed a bimodal pattern with about half of the cells displaying high V region germline identity and enrichment for unswitched IGH, while the rest of the cells carried a mutational load similar to the bulk of GC B cells and showed a switched isotype. PBL displayed a bias toward expression of IGHG and higher V region germline identity compared to the bulk of GC B cells. Genes implicated in SHM and CSR were significantly induced in specific GC subpopulations, consistent with the occurrence of SHM in dark zone cells and suggesting that CSR can occur within the GC.

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The unique biology of germinal center B cells

Cited by 127 publications

References 135 publications

Generation of High Quality Memory B Cells

Generation of High Quality Memory B Cells

Engineering optimal vaccination strategies: effects of physical properties of the delivery system on functions

Tracking Immunoglobulin Repertoire and Transcriptomic Changes in Germinal Center B Cells by Single-Cell Analysis

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