The role of B cells and Th2 cytokines in physiological and pathological inflammation

Abstract: The CD4+ T cells have an important role in inflammation. Based on the local cytokine milieu, these cells can differentiate into either a Th1 population promoting cellular immunity or Th2 population involved in humoral immunity. Th2 cells produce the anti-inflammatory cytokines IL-4 and IL-10, which might have a protective role in autoimmune diseases like rheumatoid arthritis (RA) and multiple sclerosis (MS). There are several animal models available for studying these human autoimmune diseases. Collagen-induced arthritis (CIA) and experimental-autoimmune-encephalomyelitis (EAE) are frequently used as models for RA and MS respectively. Th2 cytokines have also been suggested to be involved in mechanisms behind the prevention of fetal loss. To clarify the proposed anti-inflammatory role of Th2 cytokines in CIA and in the prevention of fetus rejection, mice deficient for IL-4 and/or IL-10 were used. During arthritis development, IL-4 showed a dualistic role. In the acute but not chronic phase of the disease, IL-4 had a pathological function. We also found that pregnancy was normal even in the absence of Th2 cytokines and Ig secreting plasma cells could be transferred from the mother to the fetus. The inflammatory process in RA and MS is also suppressed during pregnancy suggesting an anti-inflammatory role for estrogen. Physiological levels of estrogen treatment led to abrogation of CII specific T and B cell responses during CIA development. The suppressed auto reactive T cell response was neither mediated by B cells nor due to immune deviation. Similarly, estrogen had a suppressive effect on the effector phase of arthritis development. B cells play a major role in autoimmunity. However, the impact of the humoral immune response on CIA pathogenesis is frequently debated. In the present study, we demonstrate that B cells are indeed totally essential in CIA but have only a disease exacerbating role in EAE.