Elsevier

Autoimmunity Reviews

Volume 3, Issues 7–8, November 2004, Pages 516-523
Autoimmunity Reviews

Dysfunctional B cells in systemic lupus erythematosus

https://doi.org/10.1016/j.autrev.2004.07.035Get rights and content

Abstract

The classical view of B cells in the biology of autoimmune responses to infectious and self-antigens (Ag) that they promote immunity primarily by producing antibodies (Ab) is far from being complete. Indeed, studies over the last decade suggest that B cells have extraordinarily diverse functions within the immune system other than Ab production, which could contribute to autoimmunity. They normally play a role in the development of lymphoid architecture, regulating dentritic cells (DC) and T cell subsets function through cytokine production, and in activation of T cells. Receptor editing is also important in B cells which aids in immunity to infection and, possibly, prevention of autoimmunity. Both abnormalities in the distribution of B cells subsets and clinical benefit response to B cell depletion in autoimmune diseases, including systemic lupus erythematosus (SLE), highlight their pivotal function. Transgenic (Tg) animal models have shown that sensitivity of B cells to B cell Ag receptor (BCR) cross-linking is correlated to autoimmunity. Indeed, negative signaling by CD5 and other molecules, such as CD22, in maintaining tolerance through recruitment of src-homology two domain-containing protein tyrosine phosphatase-1 (SHP-1) has also been documented. In fact, we have now reached a newer area whereby B cells returned as an important contributor to autoimmune disorders.

Section snippets

Characteristics of B lymphocytes

Intriguing new insights into the multiform influences of B lymphocytes on surrounding cells have been unravelled over the past decade. They are involved in shaping lymphoid white pulp architecture, including the formation of follicular dendritic cells (DC). They also coordinate T lymphocytes and influence the pattern of immune responses through the production of cytokines both in T cells and DCs (Fig. 1).

Overactivity of B cells in systemic diseases

SLE is characterized by auto-Ab to a large assortment of nuclear Ags, including double-stranded DNA and widely expressed intracellular components, such as extractable nuclear Ags. Not long ago, evidence has been provided [22] that intracellular Ags positively select B cells to differentiate into IgM auto-Ab-secreting plasma cells. Consistent with this propensity to yield auto-Ab, B cells from patients with active SLE express activation markers, most notably CD154. Such a phenotype reflects an

Dysfunction of B cells in autoimmunity

The reasons for the selection of autoreactive B cells during development remain a subject of debate. This could be due to a defect in negative selection, resulting in aberrant survival. Altered longevity enables autoreactive B cells to escape the screening process before entry into secondary lymphoid organs (SLO) and within the GCs, due to excessive expression of Bcl-2, which is an antiapoptotic factor, or mutations in the gene of the death-inducing receptor Fas (Table 2).

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