Receptors for Ig are essential mediators of immune responses. They bridge innate and adaptive immune responses by mediating phagocytosis of opsonized pathogens, Ab-dependent cell-mediated cytotoxicity, transepithelial Ig transport, and immune complex retention by follicular dendritic cells, as well as enhancing Ag presentation and regulating leukocyte activation. IgA is the most prevalent Ig of mucosal tissue and can interact with multiple cell surface localized receptors including Fc receptor-like (FCRL) proteins, which is expressed on a subpopulation of human memory B cells of mucosa-associated lymphoid tissue. While many FCRL proteins are orphan receptors expressed by lymphocytes, recent research data confirmed that FCRL 3 and 4 can bind to IgA and is effective in the immune response. Therefore, FCRL proteins attract more attention from researchers including Creative Biolabs, a world-leading biotech company. We have put effort into the research of FCRL and we are glad to share our idea in the research of biomarkers with our peers.
Introduction of Fc Receptor-like Proteins
The FCRL family consists of six type I transmembrane receptors, the first five of which are predominantly expressed on various B lineage cell populations. The extracellular domains are composed of three to nine Ig domains with significant sequence homology to those of conventional Fc receptors for IgG and IgE isotypes and are well-conserved between humans and non-human primates.
Fig.1 Protein structure and distribution of human FCRL family members. (Li, 2014)
Function of Fc Receptor-like Proteins
Fig.2 FCRL balances immune homeostasis
and inflammation. (Agarwal, 2020)
FCRL proteins expression is almost entirely restricted to lymphocytes and is preferentially concentrated within the B lineage. While most FCRLs still remain orphan receptors, ligands for several family members have recently been discovered including IgA, IgG, MHC class II, or intracellular IgM. Given their preferential expression by B cells, it is generally accepted that FCRL proteins play a role in adaptive B cell signaling and innate-like B cell responses. Recent work has identified a role for FcRL4 as an IgA receptor, suggesting a potential function in mucosal immunity. Moreover, secretory IgA acts as a specific FCRL3 ligand while this receptor engagement mediates a transition of regulatory T cells to a pro-inflammatory Th17-like phenotype.
Fc Receptor-like Proteins and Diseases
The immunoregulatory potential of FCRL family members suggests that they may be involved in B cell-mediated disorders such as leukemias and lymphomas. Indeed, FCRL proteins are applied as biomarkers while FCRL5-positive cells could be detected in peripheral blood from hairy cell leukemia patients but not in healthy control donors. Moreover, FCRL proteins are supposed to contribute to the pathogenic potential of B cells in inflammatory diseases including rheumatoid arthritis and systemic lupus erythematosus due to their interaction with IgA and IgG. However, the mechanism of how FCRL proteins lead to immunological diseases has not been revealed.
It is gradually accepted that FCLR proteins are involved in many immunological diseases by binding autoantibodies. Hence, Creative Biolabs keeps tracking frontier research of FCLR and developing the novel application of FCLR-IgA interaction. For more details, please feel free to contact us.
References
- Li, F. J.; et al. Emerging roles for the FCRL family members in lymphocyte biology and disease. Fc Receptors. 2014, 29-50.
- Agarwal, S.; et al. Human Fc receptor-like 3 inhibits regulatory T cell function and binds secretory IgA. Cell reports. 2020, 30(5), 1292-1299.
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