B lymphocytes as antigenpresenting cells in autoimmune pathologies
DOI:
Keywords:
autoimmunity, B lymphocytes, antigen presentation, multiple sclerosis, autoimmune thyroiditis, type 1 diabetes mellitusAbstract
B cell expression of the molecules involved in antigen presentation for T cells, CD80/CD86 and HLA-DR, as well as a T lymphocyte response to exo-/auto-antigens presented by autologous B lymphocytes in mixed culture have been studied in patients with organo-specific autoimmune diseases. The increased ex vivo expression of costimulating molecule CD80 by memory B cells (CD19+CD27+) of autoimmune thyreoidite (AIT) patients was shown, as well as the in vitro amplification of the expression of CD80 (for multiple sclerosis (MS) and AIT patients) and HLA-DR (for AIT patients) in B cell polyclonal activation, which is evidence of the increasing B cell potential antigenpresenting activity in autoimmune diseases.This proposal is confirmed by a higher proliferative response of AIT patient CD4+Т lymphocytes to the exoantigen tetanus toxoid presented by autologous B lymphocytes. Besides, in AIT patients, the CD4+Т cell proliferative response to the key autoantigen, associated with the pathology, thyroid peroxidase, was higher than that of the healthy donors, though for the second autoantigen, thyroglobulin, the same effect was not revealed.Analogous investigations toward autoimmune diabetes mellitus patients have revealed the ability of B lymphocytes, preincubated with autoantigens, to induce the CD4+Т cell proliferative response, however, out of three autoantigens studied, the increased proliferation index was detected only for proinsulin, but not for insulin or glutamic acid decarboxylase. Considering the intensive B cell infiltration of autoimmune attack target tissues, which is characteristic of all the diseases investigated, the antigen presenting activity of B lymphocytes may serve as one of the mechanisms of autoimmune processes induction or progression.
References
- Armengol M.P., Juan M., Lucas-Martin A. [et al.] Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokine-containing active intrathyroidal germinal centers // Am. J. of Pathol. - 2001. - Vol. 159. - P. 861-873.
- Magliozzi R., Howell O., Vora A. [et al.] Meningeal B-cell follicles in secondary progressive multiple sclerosis associate with early onset of disease and severe cortical pathology // Brain. - 2007. - Vol. 130(4). - P. 1089-1104.
- Matsushita M., Yamamoto T., Yokozeki H. Role of cytokines and proteases in murine scleroderma // J. Med. Dent. Sci. - 2008. - Vol. 55(3-4). - P. 215-225.
- Hauser S.L., Waubant E., Arnold D.L. [et al.] B-cell depletion with rituximab in relapsing-remitting multiple sclerosis // N. Engl. J. Med. - 2008. - Vol. 358(7). - P. 676-688.
- Alexopoulos H., Kampylafka E.I., Fouka P. [et al.] Anti-aquaporin-4 autoantibodies in systemic lupus erythematosus persist for years and induce astrocytic cytotoxicity but not CNS disease // J. Neuroimmunol. - 2015. - Vol. 289. - P. 8-11.
- Braley-Mullen H., Yu S. Early requirement for B cells for development of spontaneous autoimmune thyroiditis in NOD.H-2h4 mice // J. Immunol. - 2000. - Vol. 165. - P. 7262-7269.
- Kuhle J., Pohl C., Mehling M. [et al.] Lack of association between antimyelin antibodies and progression to multiple sclerosis // N. Engl. J. Med. - 2007. - Vol. 356(4). - P. 371-378.
- Good K.L., Avery D.T., Tangye S.G. Resting human memory B cells are intrinsically programmed for enhanced survival and responsiveness to diverse stimuli compared to naive B cells // J. Immunol. - 2009. - Vol. 182(2). - P. 890-901.
- Willcox A., Richardson S.J., Bone A.J. [et al.] Analysis of islet inflammation in human type 1 diabetes // Clin. Exp. Immunol. - 2009. - Vol. 155. - P. 173-181.
- Hollsberg P., Batra V., Dressel A., Hafler D.A. Induction of anergy in CD8 T cells by B cell presentation of antigen // J. Immunol. - 1996. - Vol. 157(12). - P. 5269-5276.
- Dalai S.K., Mirshahidi S., Morrot A., Zavala F., Sadegh-Nasseri S. Anergy in memory CD4+ T cells is induced by B cells // J. Immunol. - 2008. - Vol. 181(5). - P. 3221-3231.
- Morlacchi S., Soldani C., Viola A., Sarukhan A. Self-antigen presentation by mouse B cells results in regulatory T-cell induction rather than anergy or clonal deletion // Blood. - 2011. - Vol. 118. - P. 984-991.