Defective Selection of Autoreactive B Cells in Systemic Lupus Erythematosus

In a recent review paper entitled “Defects in germinal center selection in SLE”, published in Frontiers in Immunology, the authors discuss the mechanisms leading to a deficient selection of auto-reactive B cells in lymph nodes of patients with Systemic Lupus Erythematosus (SLE).

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease, in which the immune system mistakenly recognizes healthy tissues as foreign, thus attacking them. This is caused by an auto-reactivity of B cells to the body’s own antigens. B cells undergo a selection processes that tests their tolerance for self-antigens. Only after passing this test, B cells are then released into circulation from the bone marrow. However, in SLE auto-reactive B cells are not eliminated in this step, escaping into the body. The exact causes leading to SLE development are not known, with studies showing they can be of environmental and genetic origins.

During infection, B cells bind to a foreign antigen and migrate to lymph nodes. There, in special lymphoid structures called germinal centers, B cells proliferate, differentiate and undergo mutations, maturing into plasma cells that produce antibodies against that particular antigen and memory cells that store antigen information for future encounters. During these processes, tolerance of B cells to autoantigens, i.e. to the body’s own cells, is frequently loss. Thus, before leaving germinal centers, auto-reactive cells are purged by quality control mechanisms not fully understood.

In SLE, the tolerance selection pathway in germinal centers is many times deficient. This means that antibodies against own-tissues can be produced from two sources: i) the naïve autoreactive B cell pool; and ii) non-autoreactive B cells that enter the germinal center and loose their self-tolerance while undergoing somatic mutation, not being properly eliminated by germinal center deficient tolerance selection system. In this paper, the authors present an exhaustive description of the varied mechanisms responsible for impaired germinal center selection of autoreactive B cells in SLE. Several studies targeting these deficiencies are currently ongoing, although their clinical efficacy in humans still remains untested.