Immunohistochemistry of the B‐Cell Component in Lower Lip Salivary Glands of Sjögren's Syndrome and Healthy Subjects

Abstract

Serial sections of lower lip salivary gland (LSG) biopsies were examined by immunohistochemistry, using a battery of B- and partly T-related antibodies (CD5, CD20, CD21, CD27, CD38, CD45RO, CD79a, Bcl-2 and Bcl-6) in different groups of subjects: healthy controls and clinically verified smoking or nonsmoking cases of primary Sjögren's syndrome (SS). The purpose was to characterize the B-cell pattern of the lymphocytic foci and of the tiny perivascular infiltrates preceding the development of foci. Hyperplastic tonsil was used as stain control. In normal LSG, widely dispersed CD38+ and CD79a+ as well as some CD5+ cells are a normal constituent, with lack of staining with the other antibodies. In SS/LSG, the lymphocytic foci showed staining with all the antibodies, with variable degrees of overlapping or nonoverlapping. In SS/LSG of nonsmokers, CD20+ B cells make up a prominent part of the fully developed periductal lymphocytic foci, not overlapping with CD45RO. Also, CD20+ B cells did not overlap in the infiltrates with colocalized CD27+/CD38+ cells. CD20+ B cells and CD45RO+ T cells also occur as minute infiltrates perivascularly in areas of no foci in SS/LSG as well as in SS smokers lacking the typical foci. Smokers lack foci, but tiny infiltrates express CD20 as well CD45R0. Our findings suggest that CD20+ B cells and CD45RO+ T cells are early immigrants in the LSG of SS of smokers as well as nonsmokers and that another subgroup of CD27+/CD38+ B cells gradually mix with the first two to form the characteristic foci in SS/LSG. The simultaneous demonstration of CD20+ and CD27+ B cells in SS/LSG may constitute a significant diagnostic tool. Further, the findings suggest that the early immigrating lymphocytes may have been primed at a site remote from the glands before arriving via the blood to the gland tissue.

CD38 protein deficiency induces autoimmune characteristics and its activation enhances IL‐10 production by regulatory B cells

“…There are reports where CD38 expression is increased in B and T cells from patients with LES and rheumatoid arthritis . In addition, it has been reported an increase in CD38 + CD138 + plasma cells and others subpopulations CD38 + cells from peripheral blood and lower lip salivary gland (LSG) of Sjögren′s syndrome patients (SS) . Such reports suggest that CD38 may contribute to the pathogenesis of these diseases.…”

B-cell populations and sub-populations in Sjögren's syndrome

“…This indicated the presence of a more mature subset of transitional B-cells, termed T2 B-cells, which were CD19+IgD+CD38ÀIgM+CD21+CD23+ and present within pSS salivary glands [22,24]. However, another study on lower lip salivary gland (LSG) biopsies reported that in contrast to the widely dispersed presence of B-cells expressing CD38+, CD79a+ and CD5+ to a minor degree, and lacking CD20, CD21 and CD27 in LSGs from healthy controls, LSGs from pSS patients showed CD20+ B-cells and CD27+/CD38+ B-cells, with the CD20+ B-cells being concentrated in perivascular regions that did not overlap with focal infiltrates filled with the CD27+/CD38+ B-cell subset [25]. A more recent study also detected significant numbers of CD138+, non-proliferating, Bcl-2 expressing plasma cells in the salivary glands of pSS patients with high focus scores [26].…”

A Conspicuous Role For B Cells In Sjögren’s Syndrome

“…IgD -CD38 ++ CD27 [54], which is a marker for memory B cells but is also seen in PC, in addition to genuine memory B cells, i.e., IgM-only cells with IgV gene somatic mutations [55], have been identified in the SG infiltrates. This accumulation could be caused by the ectopic expression of B cell chemokines, such as CXCL13, within the GC [56], combined with that of the CXCR5 receptor on B lymphocytes [57].…”