Effects of Breeding Environments on Generation and Activation of Autoreactive B-1 Cells in Anti-red Blood Cell Autoantibody Transgenic Mice

Murakami, Masao; Nakajima, Kazuo; Yamazaki, Ken-ichi; Muraguchi, Takehiko; Serikawa, Tadao; Honjo, Tasuku

doi:10.1084/jem.185.4.791

Cited by 84 publications

(45 citation statements)

References 18 publications

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“…Recently, it has been reported that hsp60 cross-reactive T cells mediate autoimmune pathology of the small intestine (29). In contrast to the above-mentioned studies (11)(12)(13)(14)(15)(16), in this study, we attribute reduced incidence and severity of, rather than induction of, AA to determinant mimicry.…”

Section: Discussioncontrasting

confidence: 51%

Environmental Modulation of Autoimmune Arthritis Involves the Spontaneous Microbial Induction of T Cell Responses to Regulatory Determinants Within Heat Shock Protein 65

Moudgil

Kim

Yun³

et al. 2001

The Journal of Immunology

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Both genetic and environmental factors are believed to be involved in the induction of autoimmune diseases. Adjuvant arthritis (AA) is inducible in susceptible rat strains by injection of Mycobacterium tuberculosis, and arthritic rats raise T cell responses to the 65-kDa mycobacterial heat-shock protein (Bhsp65). We observed that Fischer 344 (F344) rats raised in a barrier facility (BF-F344) are susceptible to AA, whereas F344 rats maintained in a conventional facility (CV-F344) show significantly reduced incidence and severity of AA, despite responding well to the arthritogenic determinant within Bhsp65. The acquisition of protection from AA can be circumvented if rats are maintained on neomycin/acidified water. Strikingly, naive unimmunized CV-F344 rats but not BF-F344 rats raised T cell responses to Bhsp65 C-terminal determinants (BCTD) (we have previously shown that BCTD are involved in regulation of acute AA in the Lewis rat); however, T cells of naive CV-F344 and BF-F344 gave a comparable level of proliferative response to a mitogen, but no response at all to an irrelevant Ag. Furthermore, adoptive transfer into naive BF-F344 rats of splenic cells of naive CV-F344 rats (restimulated with BCTD in vitro) before induction of AA resulted in a considerably reduced severity of AA. These results suggest that spontaneous (inadvertent) priming of BCTD-reactive T cells, owing to determinant mimicry between Bhsp65 and its homologues in microbial agents in the conventional environment, is involved in modulating the severity of AA in CV-F344 rats. These results have important implications in broadening understanding of the host-microbe interaction in human autoimmune diseases.

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Section: Discussioncontrasting

confidence: 51%

Environmental Modulation of Autoimmune Arthritis Involves the Spontaneous Microbial Induction of T Cell Responses to Regulatory Determinants Within Heat Shock Protein 65

Moudgil

Kim

Yun³

et al. 2001

The Journal of Immunology

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“…Either the cells need a stimulus, which was provided only in vitro, or they are inhibited from further differentiation or from Ab production in the PerC by an unknown mechanism. Previous reports have suggested that the expansion and activation of PerC B-1 cells may be induced by two steps in autoantibody (anti-RBC Ab) transgenic mice; enteric bacteria increase the number of PerC B-1 cells, and pathogenic infection induces PerC B-1 cells to produce anti-RBC Abs (35,36). In those transgenic mice, oral administration of LPS could induce the production of autoantibodies from PerC B-1 cells, resulting in autoimmune symptoms (35).…”

Section: Discussionmentioning

confidence: 99%

Mac-1-Negative B-1b Phenotype of Natural Antibody-Producing Cells, Including Those Responding to Galα1,3Gal Epitopes in α1,3-Galactosyltransferase-Deficient Mice

Ohdan

Swenson

Gray³

et al. 2000

The Journal of Immunology

116

119

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Human natural Abs against Galα1-3Galβ1-4GlcNAc (Gal) epitopes are a major barrier to xenotransplantation. Studies in this report, which use combined multiparameter flow cytometric sorting and enzyme-linked immunospot assay, demonstrate that anti-Gal IgM-producing cells are found exclusively in a small B cell subpopulation (i.e., CD21−/low IgMhigh B220low CD5− Mac-1− 493− cells) in the spleens of α1,3-galactosyltransferase-deficient mice. All IgM-producing cells were detected in a similar splenic subpopulation of α1,3-galactosyltransferase-deficient and wild-type mice. A higher frequency of B cells with anti-Gal surface IgM receptors was observed in the peritoneal cavity than in the spleen, but these did not actively secrete Abs, and showed phenotypic properties of B-1b cells (CD21−/low IgMhigh CD5− CD43+ Mac-1+). However, these became Mac-1− and developed anti-Gal Ab-producing activity after in vitro culture with LPS. The splenic B cells with anti-Gal receptors consisted of both Mac-1+ B-1b cells and Mac-1− B-1b-like cells. The latter comprised most anti-Gal IgM-producing cells. Our studies indicate that anti-Gal natural IgM Abs are produced by a B1b-like, Mac-1− splenic B cell population and not by plasma cells or B-1a cells. They are consistent with a model whereby B-1b cells lose Mac-1 expression upon Ag exposure and that these, rather than plasma cells, become the major IgM Ab-producing cell population.

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“…In one anti-erythrocyte Ig transgenic model (Tg), expression of the IgM Tg directs a predominant B-1 cell phenotype (24). In this model, the development and maintenance of the autoreactive B-1 cells, which leads to spontaneous autoimmune hemolytic anemia, depends on the presence of enteric bacteria, suggesting a crossreaction of self-antigen with bacteria (25). It is possible that CM22-specific B cells are also naturally preserved in normal animals by self-antigen(s) and may be also maintained by similar epitopes on enteric bacteria.…”

Section: Discussionmentioning

confidence: 99%

Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury

Zou

Austen

Chiu

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

202

205

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Reperfusion injury of ischemic tissue represents an acute inflammatory response that can cause significant morbidity and mortality. The mechanism of injury is not fully elucidated, but recent studies indicate an important role for natural antibody and the classical pathway of complement. To test the hypothesis that injury is initiated by specific IgM, we have screened a panel of IgMproducing hybridomas prepared from peritoneal cells enriched in B-1 cells. One clone, CM22, was identified that could restore pathogenic injury in RAG-1 ؊/؊ mice in an intestinal model of ischemia͞reperfusion (I͞R). In situ activation of the classical pathway of complement was evident by deposition of IgM, complement C4, and C3 in damaged tissue after passive transfer of CM22 IgM. Sequence analysis of CM22 Ig heavy and light chains showed germ-line configurations with high homology to a V H sequence from the B-1 repertoire and a VK of a known polyreactive natural IgM. These data provide definitive evidence that I͞R injury can be initiated by clonally specific natural IgM that activates the classical pathway of complement. This finding opens an avenue for identification of I͞R-specific self-antigen(s) and early prevention of injury.

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Effects of Breeding Environments on Generation and Activation of Autoreactive B-1 Cells in Anti-red Blood Cell Autoantibody Transgenic Mice

Cited by 84 publications

References 18 publications

Environmental Modulation of Autoimmune Arthritis Involves the Spontaneous Microbial Induction of T Cell Responses to Regulatory Determinants Within Heat Shock Protein 65

Environmental Modulation of Autoimmune Arthritis Involves the Spontaneous Microbial Induction of T Cell Responses to Regulatory Determinants Within Heat Shock Protein 65

Mac-1-Negative B-1b Phenotype of Natural Antibody-Producing Cells, Including Those Responding to Galα1,3Gal Epitopes in α1,3-Galactosyltransferase-Deficient Mice

Identification of a specific self-reactive IgM antibody that initiates intestinal ischemia/reperfusion injury

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