The biological roles of B cell membrane proteins in the FCRL family are enigmatic. FCRL proteins, including FCRL5, were shown to modulate early BCR signaling, although the subsequent, functional consequences of receptor engagement are poorly understood. We found that FCRL5 surface protein itself was induced temporarily upon BCR stimulation of human, naive B cells, indicating precise control over timing of FCRL5 engagement. Cross-linking of FCRL5 on cells induced to express FCRL5 enhanced B cell proliferation significantly. This enhancement required costimulation of the BCR and TLR9, two signals required for optimal proliferation of naive B cells, whereas T cell help in the form of anti-CD40 and IL-2 was dispensable. In addition, we found that FCRL5 stimulation generated a high proportion of cells displaying surface IgG and IgA. Optimal development of cells expressing switched isotypes required T cell help, in addition to stimuli found necessary for enhanced proliferation. Surprisingly, cells that developed upon FCRL5 stimulation simultaneously displayed surface IgM, IgG, and IgA. Cells expressing multiple Ig isotypes were described in hairy cell leukemia, a disease in which FCRL5 is overexpressed. Enhanced proliferation and downstream isotype expression upon FCRL5 stimulation could reflect a physiological role for FCRL5 in the expansion and development of antigen-primed B cells. In addition, FCRL5 may promote growth of malignant cells in hairy cell leukemia and other FCRL5-expressing tumors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1189/jlb.0211096 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Humoral responses are enhanced by facilitating B cell viability by Fcrl5 overexpression in B cells.
Int Immunol
September 2024
Division of Immunology and Genome Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed in naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab) production in both T cell-independent type 1 (TI1) and T cell-dependent (TD) responses.
View Article and Find Full Text PDFRegulation of B-cell function and expression of CD11c, T-bet, and FcRL5 in response to different activation signals.
Eur J Immunol
August 2024
Division of Infectious Diseases, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
CD11c, FcRL5, or T-bet are commonly expressed by B cells expanding during inflammation, where they can make up >30% of mature B cells. However, the association between the proteins and differentiation and function in the host response remains largely unclear. We have assessed the co-expression of CD11c, T-bet, and FcRL5 in an in vitro B-cell culture system to determine how stimulation via the BCR, toll-like receptor 9 (TLR9), and different cytokines influence CD11c, T-bet, and FcRL5 expression.
View Article and Find Full Text PDFCD4 T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE.
Lupus Sci Med
September 2022
Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand
Objective: To explore cooperation between activated naïve (aNAV) B cells and CD4 T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion.
Methods: Peripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects.
Presence and possible impact of Fcγ receptors on resident kidney cells in health and disease.
Immunol Cell Biol
September 2022
Department of Pulmonology, Medical University of Gdansk, Gdansk, Poland.
Fcγ receptors (FcγRs) bind the Fc fragment of immunoglobulin G (IgG), mostly after IgG opsonizes a bacterial or viral antigen or danger/damage-associated molecule. Consequently, classic FcγRs initiate phagocytosis of the IgG-antigen immune complex and stimulate an immune reaction against the threat. Signals from activating FcγRs (FcγRI, FcγRIIa/c, FcγRIIIa/b) are balanced by inhibitory FcγRIIb and likely also by two FcR-like proteins (FCRL4 and FCRL5).
View Article and Find Full Text PDFInterferon-γ signal drives differentiation of T-bet atypical memory B cells into plasma cells following Plasmodium vivax infection.
Sci Rep
March 2022
Department of Clinical Microbiology and Applied Technology, Faculty of Medical Technology, Mahidol University, Bangkok, 10700, Thailand.
For development of a long-lasting protective malaria vaccine, it is crucial to understand whether Plasmodium-induced memory B cells (MBCs) or plasma cells develop and stably contribute to protective immunity, or on the contrary the parasite suppresses antibody responses by inducing MBC dysfunction. The expansion of T-bet atypical MBCs is described in chronic Plasmodium falciparum-exposed individuals. However, it remains unclear whether accumulation of T-bet atypical MBCs is indicative of a protective role or rather an impaired function of the immune system in malaria.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!