A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues

Sakamoto, Norihisa; Shibuya, Kazuko; Shimizu, Yoshio; Yotsumoto, Katsumi; Miyabayashi, Tomoyuki; Sakano, Seiji; Tsuji, Takao; Nakayama, Eiichi; Nakauchi, Hiromitsu; Shibuya, Akira

doi:10.1002/1521-4141(200105)31:5<1310::aid-immu1310>3.0.co;2-n

Cited by 105 publications

(71 citation statements)

References 34 publications

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“…However, polyclonal IgM may have an advantage even in this situation if a putative Fc R binds preferentially to the altered confirmation arising out of IgM complexed with Ag. An Fc R has been described, although not with these properties (21). However, a recent report has demonstrated that serum IgM is a ligand for CD19 (22), and B1 and MZ B cells are affected by alterations in CD19 expression (8,23).…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM

Baker

Ehrenstein

2002

The Journal of Immunology

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Natural IgM has a wide range of actions in the immune system. Here we demonstrate that mice lacking serum IgM have an expansion in splenic marginal zone B cells with a proportionately smaller reduction in follicular B cells. The increase in the marginal zone-follicular B cell ratio (and an expansion in peritoneal B1a cells) is fully reversed by administration of polyclonal IgM, but not by two IgM monoclonals. Mice engineered to have a secreted oligoclonal IgM repertoire with an endogenous membrane IgM also exhibited a similar expansion of marginal zone B cells. We propose that natural IgM, by virtue of its polyreactivity, enhances Ag-driven signaling through the B cell receptor and promotes the formation of follicular B cells. These results demonstrate that natural IgM regulates the selection of B lymphocyte subsets.

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Section: Discussionmentioning

confidence: 99%

Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM

Baker

Ehrenstein

2002

The Journal of Immunology

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“…However, alternative receptors for IgA have been identified in mice. Indeed, on murine B cells and macrophages, a receptor specific for both IgA and IgM Fc (Fcα/µ) has been characterised [89,93]. It is only recently that the first true orthologues of human FcαR have been described in rats [58], cattle [67] and macaques [87].…”

Section: Function Of Iga In Serum and Mucosamentioning

confidence: 99%

The IgA system: a comparison of structure and function in different species

2006

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-The predominant immunoglobulin isotype on most mucosal surfaces is secretory immunoglobulin A (SIgA), a polypeptide complex comprising two IgA monomers, the connecting J chain, and the secretory component. The molecular stability and strong anti-inflammatory properties make SIgA particularly well suited to provide protective immunity to the vulnerable mucosal surfaces by preventing invasion of inhaled and ingested pathogens. In contrast to SIgA, IgA in serum functions as an inflammatory antibody through interaction with FcαR on immune effector cells. Although IgA appears to share common features and protective functions in different species, significant variations exist within the IgA systems of different species. This review will give an overview of the basic concepts underlying mucosal IgA defence which will focus on the variations present among species in structure, antibody repertoire development, pIgR-mediated transport, colostral IgA content, hepatobiliary transport, and function with particular emphasis on the IgA system of the pig and dog. These interspecies variations emphasise the importance of elucidating and analysing the IgA system within the immune system of the species of interest rather than inferring roles from conclusions made in human and mouse studies.

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“…However, it is important to note that B1 cells predominantly release multivalent IgM which do not bind to the FcgR. Instead, IgM bind to the Fcm receptor also expressed on Mf [43,44]. Therefore, we investigated whether B1-cell-derived IgM could induce M2 polarization of Mf.…”

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Macrophage polarization to a unique phenotype driven by B cells

et al. 2010

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Regulation of adaptive immunity by innate immune cells is widely accepted. Conversely, adaptive immune cells can also regulate cells of the innate immune system. Here, we report for the first time the essential role of B cells in regulating macrophage (M/) phenotype. In vitro B cell/M/ co-culture experiments together with experiments in transgenic mice models for B-cell deficiency or overexpression showed B1 cells to polarize M/ to a distinct phenotype. This was characterized by downregulated TNF-a, IL-1b and CCL3, but upregulated IL-10 upon LPS stimulation; constitutive expression of M2 M/ markers (e.g. Ym1, Fizz1) and overexpression of TRIF-dependent cytokines (IFN-b, CCL5). Mechanistically, this phenotype was linked to a defective NF-jB activation, but a functional TRIF/STAT1 pathway. B1-cell-derived IL-10 was found to be instrumental in the polarization of these M/. Finally, in vivo relevance of B1-cell-induced M/ polarization was confirmed using the B16 melanoma tumor model where adoptive transfer of B1 cells induced an M2 polarization of tumor-associated M/. Collectively, our results define a new mechanism of M/ polarization wherein B1 cells play a key role in driving M/ to a unique, but M2-biased phenotype. Future studies along these lines may lead to targeting of B1 cells to regulate M/ response in inflammation and cancer. Supporting Information available online IntroductionMacrophages (Mf) are a heterogeneous cell population involved in diverse physiological processes including anti-microbial defence, wound resolution, inflammation, tissue remodeling, plaque formation in atherosclerosis and promotion of tumor growth [1][2][3][4][5][6][7]. Despite their heterogeneity, Mf can be broadly divided into M1 (classically activated) or M2 (alternatively activated) phenotypes [1,[8][9][10][11][12]. The M1 phenotype is induced in response to microbial products such as LPS or proinflammatory cytokines including IFN-g, IL-1b or TNF-a. M1 Mf produce further proinflammatory cytokines (TNF-a, IL-12 and CCL3) with reactive oxygen and nitrogen intermediates, which combine to give M1 Mf potent antimicrobial, tumoricidal and inflammatory properties [12]. In contrast, the M2 phenotype results from exposure to antiinflammatory molecules such as glucocorticoid hormones, IL-4, Ã These authors contributed equally to this work. 2296IL-13, IL-10 or immune complexes [10][11][12]. M2 Mf are antiinflammatory and immunosuppressive in nature. They are highly phagocytic, preferentially activate the arginase pathway, promote angiogenesis, tissue remodeling and have pro-tumoral activity [8,12]. However, in vivo, the division between M1 and M2 cells may be blurred, with the above phenotypes likely representing two extremes in a continuum of Mf functional states [9,[13][14][15].Transcriptome data demonstrate the existence of distinct polarization phenotypes for Mf associated with specific pathological conditions [4,7,[16][17][18]. Based on this, it is believed that the phenotype of an Mf is a reflection of its immediate microenvironment....

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A novel Fc receptor for IgA and IgM is expressed on both hematopoietic and non-hematopoietic tissues

Cited by 105 publications

References 34 publications

Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM

Cutting Edge: Selection of B Lymphocyte Subsets Is Regulated by Natural IgM

The IgA system: a comparison of structure and function in different species

Macrophage polarization to a unique phenotype driven by B cells

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