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Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [RNA-Seq]

ABSTRACT: We performed NGS on Ig heavy chain V sequences amplified from RNA obtained from human tonsillar B cell subsets. From these NGS data, we reconstructed ongoing B cell responses as lineage trees, providing crucial in vivo developmental context. Each memory subset typically maintained its lineage, denoting mechanisms enforcing their phenotypes. FCRL4-FCRL5+ cells were the most represented memory subset in lineage trees, indicating robust participation in ongoing responses. Affinity maturation of both FCRL4-FCRL5+ and FCRL4+FCRL5+ atypical memory cells was stalled in chronic streptococcus infection, conceivably due to negative feedback from IgG immune complexes. We propose that FCRL4 and FCRL5 function as sensors of immune complexes, thus controlling atypical memory B cell responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE145519 | GEO | 2020/08/04

REPOSITORIES: GEO

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Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [array]

Project description:We performed gene array analysis of three memnory cell subsets sorted from three tonsil donors with the following patterns of surface expression: FCRL4-, FCRL5+ (designated F5), FCRL4 -, FCRL 5- (designated DN) , and FCRL4+, FCRL5+ (designated DP). The three memory subsets were clearly segregated by principal component analysis and cluster analysis as distinct, and hundreds of genes were found differentially expressed. between any two subsets

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Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells

Project description:Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells

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Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [array]

Project description:Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [array]

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Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [RNA-Seq]

Project description:Fc receptor-like 4 (FCLR4) and Fc receptor-like receptor 5 (FCRL5) define and control human atypical memory B cells [RNA-Seq]

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The memory B cell response to influenza vaccination is impaired in older persons

Project description:Influenza imparts an age-related increase in mortality and morbidity. The most effective countermeasure is vaccination; however, vaccines offer modest protection in older adults. To investigate how ageing impacts the memory B cell response we tracked haemagglutinin specific B cells by indexed flow sorting and single cell RNA sequencing in twenty healthy adults administered the trivalent influenza vaccine. We found age-related skewing in the memory B cell compartment six weeks after vaccination, with younger adults developing haemagglutinin specific memory B cells with an FCRL5+ “atypical” phenotype, showing evidence of somatic hypermutation and positive selection, which happened to a lesser extent in older persons. We confirmed the germinal center ancestry of these FCRL5+ “atypical” memory B cells using scRNASeq from fine needle aspirates of influenza responding human lymph nodes and paired blood samples. Together, this study shows that the aged human germinal center reaction and memory B cell response following vaccination is defective.

2021-03-05 | GSE167823 | GEO

Plasmodium-specific atypical memory B cells are short-lived activated B cells

Project description:Chronic infections such as HIV, tuberculosis and malaria in humans are associated with the appearance of atypical memory B cells in peripheral blood. It has been suggested that these B cells do not function normally as memory cells, and thus may be responsible for poor acquisition of immunity and maintenance of chronic infections. Studies on these cells in human infections are limited by the lack of accessibility to lymphoid organs, and relevant mouse models would be valuable to investigate their development, functional capacities, and role. To investigate Plasmodium-specific memory B-cell responses during malaria, we generated an immunoglobin heavy chain knock-in mouse with a B-cell receptor that recognizes the merozoite surface protein (MSP)-1 of the rodent malaria parasite, Plasmodium chabaudi. Using this mouse and a P. chabaudi infection initiated by infected mosquito bites we show that antigen-specific B cells with many characteristics of human atypical memory B cells are generated. These cells are immunoglobulin class-switched and express, among others, the cell surface molecules CD11c, CD11b, FCRL5, and some inhibitory receptors including PD1 and LAIR-1, as well as the transcription factor T-bet. Antigen-specific atypical memory B cells are detected side-by-side with classical memory B cells during chronic blood-stage infection. Whereas classical memory B cells persist after complete infection clearance, atypical memory B cells are short-lived and disappear from the spleen at the resolution of chronic infection. Short-lived Plasmodium-specific atypical B cells also appear transiently after immunization with a TLR7/8 ligand and MSP-1. Our data suggest that these atypical memory B cells are not a subset of memory B cells, but rather antigen-experienced activated cells, and part of a normal ongoing response. Their persistence over weeks in malaria and other infections may be a consequence of continued and chronic antigenic stimulation.

2018-11-01 | GSE115155 | GEO

Expansion of an FCRL5+ B cell subset resembling atypical memory B cells in an animal model of malaria

Project description:Background: In human malaria, parasites of the genus Plasmodium elicit expansion of atypical memory B cells (atMBCs), which lack the classical markers CD21 and CD27. We have identified a putative population of analogous B cells in a murine model of infection with P. chabaudi, delineated by the marker FCRL5. We performed RNA-Seq on FCRL5+ and FCRL5- B cells sorted from infected mice, so as to characterize the transcriptional profile of these cells and permit comparison to atMBCs in humans. Results: FCRL5+ B cells were found to have distinct transcriptional profiles from FCRL5- B cells, with approximately 400 genes exhibiting significant differences between the two groups. Additionally, about 25% of these differentially expressed genes were also differentially expressed in human atMBCs versus classical MBCs, as previously described by Sullivan et al (PLoS Pathogens 2015). Conclusions: FCRL5+ class-switched B cells are a transcriptionally distinct subset arising in P. chabaudi infection, with transcriptional similarities to human atMBCs that develop in chronic malaria settings.

2019-04-16 | GSE85205 | GEO

B cells expressing the IgA receptor FcRL4 participate in the autoimmune response in patients with rheumatoid arthritis

Project description:The clinical efficacy of B cell targeting therapies highlights the pathogenic potential of B cells in inflammatory diseases. Expression of Fc Receptor like 4 (FcRL4) identifies a memory B cell subset, which is enriched in the joints of patients with rheumatoid arthritis (RA) and in mucosa-associated lymphoid tissue. The high level of RANKL production by this B cell subset indicates a unique pathogenic role. In addition, recent work has identified a role for FcRL4 as an IgA receptor, suggesting a potential function in mucosal immunity. Here, the contribution of FcRL4+ B cells to the specific autoimmune response in the joint of patients with RA was investigated. Single FcRL4+ and FcRL4- B cells were sorted from synovial fluid and tissue from RA patients and their immunoglobulin genes characterized. Levels of hypermutation in the variable regions in both populations were largely consistent with memory B cells selected by an antigen- and T cell-dependent process. Recombinant antibodies were generated based on Ig variable region sequences and investigated for antigen specificity. A significantly larger proportion of the recombinant antibodies generated from the IgH and IgL variable regions of individual synovial FcRL4+ B cells showed reactivity towards citrullinated autoantigens. Furthermore, both in analyses based on heavy chain sequences and flow cytometric detection, these cells have significantly increased usage of the IgA isotype. Their low level of expression of immunoglobulin and plasma cell differentiation genes does not suggest current antibody secretion. We conclude that these activated B cells are a component of the local autoimmune response, and through their RANKL expression, can contribute to joint destruction. Furthermore, their expression of FcRL4 and their enrichment in the IgA isotype points towards a potential role in the link between mucosal and joint inflammation for these cells.

2017-03-31 | GSE94897 | GEO

Molecular and phenotypic characterization of a preplasmablast population in the process of differentiation of human B cells to plasma cells

Project description:In vitro differentiation of human memory B cells into preplasmablasts and FCRL4 B cells

2011-03-01 | E-MEXP-3034 | biostudies-arrayexpress

Characterization of human Fcrl4-positive B cells

Project description:FCRL4 is an immunoregulatory receptor that belongs to the Fc receptor-like (FCRL) family. In healthy individuals, this protein is specifically expressed by memory B cells (MBCs) and is preferentially localized in subephitelial regions of lymphoid tissues. An expansion of FCRL4+ B cells has been shown in blood or other tissues in various infectious or autoimmune pathologies. In the present work, we generated and characterized in vitro FCRL4+ B cells from purified MBCs using T-dependent and/or T-independent stimulation. FCRL4+ B cells account for 17% of cells generated at day-4 of culture. Transcriptomic and phenotypic analysis of FCRL4+ cells show that they are closely related to FCRL4+ tonsillar MBCs. Interestingly, these cells highly express inhibitory receptors genes as described for exhausted FCRL4+ MBCs in the blood of HIV-viremic individuals. In agreement, in vitro generated FCRL4+ B cells show a significant underexpression of cell cycle genes with a two fold weaker number of cell division compared to FCRL4- cells. Finally, resulting from their reduced proliferation and differentiation potential, we show that FCRL4+ cells are not prone to generate plasma cells, contrary to FCRL4- cells. Given the difficulty to access to in vivo FCRL4+ cells, our in vitro model could be of major interest to study the biology of normal and pathological FCRL4+ cells.

2017-04-30 | GSE87384 | GEO

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