Elsevier

Autoimmunity Reviews

Volume 9, Issue 9, July 2010, Pages 600-603
Autoimmunity Reviews

Review
What do we know about memory B cells in primary Sjögren's syndrome?

https://doi.org/10.1016/j.autrev.2010.05.005Get rights and content

Abstract

Abnormalities of memory B cells seem to be closely involved in the pathogenesis of primary Sjögrens Syndrome (pSS) and its malignant complication, B cell lymphoma. Recent studies on B cells in pSS add to our understanding of the distinct memory B cell subsets in pSS. Reduction of peripheral memory CD27+ B cells, most strikingly of the CD27+IgM+ subset, may indicate a lack of appropriate censoring mechanisms and incomplete differentiation processes within the ectopic lymphoid tissues in pSS. This ectopically formed lymphoid tissue might protect autoreactive memory B cells from deletion by physiological check-points and, thereby, may contribute to the perpetuation of the disease as well as to an enhanced lymphoma risk. Thus, B cells may be potential targets of direct or indirect treatment in pSS.

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

  • Derangement of memory B cells is a hallmark of pSS

  • Distinct memory B cell subsets have been identified in pSS

  • Recent studies underline the potential role of memory B cells in the pathogenesis of the disease, pSS, and its malignant complications.

  • 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

References (40)

  • J.O. Bohnhorst et al.

    Significantly depressed percentage of CD27+ (memory) B cells among peripheral blood B cells in patients with primary Sjögren's syndrome

    Scand J Immunol

    (2001)
  • A. Hansen et al.

    Diminished peripheral blood memory B cells and accumulation of memory B cells in the salivary glands of patients with Sjögren's syndrome

    Arthritis Rheum

    (2002)
  • A. Hansen et al.

    B cell lymphoproliferation in chronic inflammatory rheumatic diseases

    Nat Clin Pract Rheumatol

    (2007)
  • C. Daridon et al.

    Identification of transitional type II B cells in the salivary glands of patients with Sjögren's syndrome

    Arthritis Rheum

    (2006)
  • A. Hansen et al.

    Peripheral CD27+ IgD + IgM + B cells in patients with primary Sjögrens syndrome and healthy donors

    Ann Rheum Dis

    (2009)
  • J.O. Pers et al.

    BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome

    Arthritis Rheum

    (2007)
  • U. Klein et al.

    Human immunoglobulin (Ig)M + IgD + peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes: CD27 as a general marker for somatically mutated (memory) B cells

    J Exp Med

    (1998)
  • J.C. Weill et al.

    Human marginal zone B cells

    Annu Rev Immunol

    (2009)
  • S.G. Tangye et al.

    Human IgM + CD27+ B cells: memory B cells or “memory” B cells?

    J Immunol

    (2007)
  • J.F. Fecteau et al.

    A new memory CD27  IgG + B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation

    J Immunol

    (2006)
  • Cited by (28)

    • Insight into pathogenesis of Sjögren's syndrome: Dissection on autoimmune infiltrates and epithelial cells

      2017, Clinical Immunology
      Citation Excerpt :

      Thus, SGEC have been shown able to mediate the activation of naïve CD4+-T cells [90] and to promote their differentiation into functional follicular TFH cells through IL-6 and ICOSL expression [109]. The epithelial expression of functional BAFF [71,78] suggests that SGECs may also be directly involved in the SS-associated altered B cell differentiation [39,110] and formation of ectopic GC-like structures [111]. Indeed, in accordance with MSG findings, co-culture with SGEC resulted in a switch of peripheral blood B cells towards TII-like, early Bm5 and Bm2 B cells with concominant decrease of the Bm1 subpopulation [112].

    • Glandular Epithelium: Innocent Bystander or Leading Actor?

      2016, Sjogren's Syndrome: Novel Insights in Pathogenic, Clinical and Therapeutic Aspects
    • Follicular helper T cells may play an important role in the severity of primary Sjögren's syndrome

      2013, Clinical Immunology
      Citation Excerpt :

      B cell hyperreactivity, development of autoantibodies, and disturbance in distribution of B cell subtypes on the periphery are characteristics in pSS. Levels of circulating IgM and IgG memory B cells are decreased in peripheral blood; on the contrary their proportions are elevated in the inflamed tissues, especially in salivary glands [2,34–37]. Our results support partially the aforementioned observations, since we found a negative correlation between the proportions of TFH cells and IgM and IgG memory B cells in the peripheral blood.

    • A chronic nonhealing gingival mass

      2013, Journal of the American Dental Association
      Citation Excerpt :

      Lymphomas have many different forms and presentations, including oral mucosal involvement and ulceration.24 Factors influencing this diagnosis include previous radiation therapy, an autoimmune disease such as Sjögren syndrome or immunosuppressive therapy.25 Malignant lymphomas often are found in the maxillofacial area; however, primary gingival involvement is uncommon.24

    View all citing articles on Scopus
    View full text