Catalytic antibodies in the bone marrow and other organs of Th mice during spontaneous development of experimental autoimmune encephalomyelitis associated with cell differentiation.

Exact mechanisms of autoimmune disease development are still yet unknown. However, it is known that the development of autoimmune diseases is associated with defects in the immune system, namely, the violation of the bone marrow hematopoietic stem cells (HSCs) differentiation profiles. Different characteristics of autoimmune reaction development in experimental autoimmune encephalomyelitis (EAE) prone Th mice characterizing T-lymphocytes response were analyzed using standard approaches. Profiles of several HSCs differentiation of bone marrow (BFU-E, CFU-E, CFU-GM, CFU-GEMM, T- and B-lymphocytes) of Th male and female mice during spontaneous development of EAE were noticeably different. Patterns of total lymphocytes, B- and T-cells proliferation in several different organs (bone marrow, blood, spleen, thymus, and lymph nodes) were also remarkably different. In addition, there were in time noticeable differences in their changes for some organs of male and female mice. Characters of changes in the profiles of CD4 and CD8 cells proliferation in some organs not always coincide with those for total T lymphocytes. The changes in the differentiation profiles of HSCs and the level of lymphocytes proliferation in the bone marrow and other organs were associated with the increase in the concentration of antibodies against DNA, myelin basic protein, and myelin oligodendrocyte glycoprotein, and catalytic antibodies hydrolyzing these substrates. Despite some differences in changes in the analyzed parameters, in general, the spontaneous development of EAE in male and female mice occurs to some extent in a comparable way.

Production of Abzymes in Th, CBA, and C57BL/6 Mice before and after MOG Treatment: Comparing Changes in Cell Differentiation and Proliferation.

Till yet there is no data concerning mechanisms of autoimmune diseases development. Experimental autoimmune encephalomyelitis (EAE) prone C57BL/6 (T- and B-lymphocyte response), non-autoimmune CBA, and Th mice with T cell response were immunized with myelin oligodendrocyte glycoprotein (MOG35-55) to compare different characteristics of autoimmune reaction development. Bone marrow differentiation profiles of hematopoietic stem cells (HSCs), lymphocyte proliferation in various organs associated with the production of antibodies against DNA, myelin basic protein (MBP), and MOG, as well as abzymes hydrolyzing these antigens, were analyzed before and after immunization. Profiles of HSC differentiation [BFU-E (erythroid burst-forming unit (early erythroid colonies), CFU-E (erythroid burst-forming unit (late erythroid colonies), CFU-GM (granulocytic-macrophagic colony-forming unit), and CFU-GEMM granulocytic-erythroid-megakaryocytic-macrophagic colony-forming unit] and patterns of lymphocyte proliferation in different organs (brain, spleen, thymus, and lymph nodes) were very different for C57BL/6, CBA, and Th mice. We conclude that only C57BL/6 mice were predisposed to spontaneous and MOG-induced acceleration of EAE development. CBA mice are not prone to the development of autoimmune reactions. After immunization, Th mice demonstrate changes in several parameters similar to C57BL/6 and other to CBA mice; Th mice are more prone to developing autoimmune reactions than CBA mice. Our data may be important for understanding the combined presence in mice lymphocytes with T and B cell responses for spontaneous and induced autoimmune diseases.