ReviewWhat do we know about memory B cells in primary Sjögren's syndrome?
Introduction
Primary Sjögren´s syndrome (pSS) is a chronic inflammatory autoimmune disease of as yet unknown origin [1], [2]. Preferentially, pSS affects exocrine glands such as salivary and lacrimal glands resulting in keratoconjunctivitis sicca and xerostomia. But, there is also a wide range of clinical and laboratory manifestations, emphasizing that pSS is a systemic disorder [1], [2]. Although the process that underlies the autoimmune response in pSS is not known, it is well established that close interactions of salivary gland epithelial cells, endothelial cells and dendritic cells with the infiltrating lymphoid cells contribute to the perpetuation and progression of the disease as well as to systemic lymphocyte derangement [3]. In this regard, hallmarks of pSS are B cell hyperactivity and B cell disturbances as manifested by hypergammaglobulinemia, circulating autoantibodies and/or immune complexes, changes in the distribution of peripheral B cell subsets [4], [5], [6], formation of germinal center (GC)-like structures within the inflamed tissues, and, finally, an enhanced risk to develop B cell lymphoma [1], [7]. More detailed analyses of B cell subsets in pSS [8], [9], [10] as well as first data on B cell repopulation following B cell depletion therapy with rituximab in pSS patients [11] have underlined the central role of B cells, especially of the memory B cell compartment, in the immunopathogenesis of pSS.
Section snippets
Memory B cell subsets in pSS
A considerably heterogeneity is apparent among human memory B cells which account for about 40 to 60% of all peripheral blood B cells in human adults [9], [12], [13], [14], [15], [16], [17]. Notably, the circulating peripheral blood memory B cell repertoire may reflect complex influences on differentiation, activation, selection, homing and recirculation of B cells from lymphoid organs and tissues. Altered B cell differentiation and priming, shedding of surface CD27 molecules, accumulation of
B cell depletion with rituximab in pSS
B cell depletion therapy with rituximab (anti-CD20 antibody) have shown beneficial effects in the treatment of pSS patients, both with or without associated B cell lymphoma [32], [33]. Moreover, immunohistological analyses of the primary effects as well as of the B cell restoration after B cell depletion therapy with rituximab have provided important information on the pathology of B cell disturbances in pSS. In more detail, following rituximab treatment, the lymphocytic infiltrates of pSS
B cell lymphomas in pSS
It is well established that a subset of patients with primary Sjögrens syndrome is at enhanced risk to develop B cell lymphomas [34], [35], most frequently diffuse large B cell lymphoma (DLBCL) or marginal-zone B cell lymphoma (MZL) of the mucosa associated lymphoid tissue (MALT)-type [7], [36]. Notably, for both lymphoma entities a GC or post-GC origin of lymphoma development has been suggested [7]. Thus, derangement of GC or memory B cell development in pSS may prone to lymphoma development
Conclusions
Recent studies on B cell disturbances in pSS underline the role of distinct memory B cell subsets in the immunopathogenesis of the disease. B cells seem to be closely involved in the formation of ectopic lymphoid tissue in the inflamed salivary glands which, later on, contributes to the characteristic memory B cell abnormalities found in pSS as well as to its malignant complication, B cell lymphoma. Therefore, B cells may be potential targets of direct or indirect treatment in pSS [38], [39],
Take-home messages
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Derangement of memory B cells is a hallmark of pSS
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Distinct memory B cell subsets have been identified in pSS
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Recent studies underline the potential role of memory B cells in the pathogenesis of the disease, pSS, and its malignant complications.
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First data on B cell depletion therapy with rituximab in pSS patients with or without associated B cell lymphoma indicate beneficial effects on salivary gland lesions and function
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