MHC class I family proteins retard systemic lupus erythematosus autoimmunity and B cell lymphomagenesis

• Published in: The Journal of immunology (1950) 2011-11, Vol.187 (9), p.4695-4704
• Main Authors: McPhee, Caroline G, Sproule, Thomas J, Shin, Dong-Mi, Bubier, Jason A, Schott, William H, Steinbuck, Martin P, Avenesyan, Lia, Morse, 3rd, Herbert C, Roopenian, Derry C
• Format: Article
• Language: English
• Subjects: Animals; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - pathology; beta 2-Microglobulin - deficiency; beta 2-Microglobulin - genetics; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; H-2 Antigens - genetics; Histocompatibility Antigen H-2D; Histocompatibility Antigens Class I - genetics; Histocompatibility Antigens Class I - physiology; Killer Cells, Natural - immunology; Killer Cells, Natural - pathology; Lupus Erythematosus, Systemic - immunology; Lupus Erythematosus, Systemic - mortality; Lupus Erythematosus, Systemic - prevention & control; Lymphoma, B-Cell - immunology; Lymphoma, B-Cell - mortality; Lymphoma, B-Cell - prevention & control; Mice; Mice, Inbred Strains; Moloney murine leukemia virus - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1101776

Dysregulation of the T cell-dependent Ab response can lead to numerous immunological disorders, ranging from systemic lupus erythematosus to B cell lymphomas. Cellular processes governed by MHC class II proteins play a major role in this response and its dysregulation. The extent to which processes controlled by the diverse family of MHC class I proteins impact such autoimmune and neoplastic disorders, however, is less clear. In this study, we genetically dissect the contributions of individual MHC class I family members and the pathological processes under their control in the systemic lupus erythematosus-like disease of BXSB.Yaa mice and B cell lymphomagenesis of SJL mice. This study reveals a powerful repressive regulatory axis comprised of MHC class I-dependent CD8(+) T cells and NK cells. These results indicate that the predominant role of the MHC class I protein family in such immunological disorders is to protect from more aggressive diseases.