Polyclonally triggered B cells in the peripheral blood and bone marrow of normal individuals and in patients with systemic lupus erythematosus and primary sjögren's syndrome

Abstract

Numbers of B cells spontaneously secreting Ig (IgC, IgA, and IgM) were determined by a plaque-forming cell (PFC) assay simultaneously in the peripheral blood and bone marrow of normal individuals, patients with systemic lupus erythematosus (SLE), and patients with primary Sjogren's syndrome. Normal individuals had 382 (f 89) PFC per 106 mononuclear cells in peripheral blood. Patients with either active or inactive Sjcigren's syndrome had normal numbers of spontaneous Ig-secreting cells in peripheral blood (P > 0.2). Conversely, patients with inactive as well as active SLE had markedly increased spontaneous PFC (P < 0.05 and P c 0.001, respectively). Patients with active SLE had significantly greater PFC than patients with inactive SLE: 3,984 (+ 960) versus 1,605 (+ 527) PFC per 106 mononuclear cells (P < 0.05). The lack of increased numbers of activated B cells in the blood of patients with Sjogren's syndrome was not explained by a preferential sequestration of activated B cells in the bone marrow. However, of particular interest was the finding that the bone marrow served not only as a major source of virgin B cells but as a lymphoid organ of either in situ Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by bone marrow-derived (B) cell hyperreactivity with hypergammaglobulinemia and autoantibody production (1-5). In addition, abnormalities of thymus-derived (T) cell subsets, particularly a deficiency of suppressor T cells, have been reported in a number of studies (reviewed in reference 5). This association of hyperactive B cells and irnmunoregulatory T cell abnormalities is strongly analogous to the murine models of SLE (6,7). It has been unclear whether the B cell hyperreactivity in SLE is independent from and actually may precede the T cell abnormalities or whether the B cell hyperreactivity results from deficient suppressor cell activity. Of interest in this regard is the fact that certain studies in the murine mod-

Evidence for coxsackievirus infection in primary Sjögren's syndrome

“…Concordant with this hypothesis, preliminary results of RT-PCR performed on peripheral blood mononuclear cells from 3 patients with chronic primary SS were negative for coxsackieviral genomic sequences, while RT-PCR performed on MSG biopsy samples isolated simultaneously from the same 3 patients yielded positive results (data not shown). Moreover, it has previously been reported that peripheral blood B lymphocytes in primary SS are not activated, while B lymphocytes of exocrine glands are highly activated (15). Finally, a preliminary screening of 18 patients with primary SS and 20 healthy controls for the presence of circulating "protective" antibodies against several coxsackievirus B serotypes (B1, B2, B3, B4, B5) indicated a small, although not statistically significant, increase in these antibodies in patients with primary SS (data not shown).…”

Spontaneous class switching and B cell hyperactivity increase autoimmunity against intracellular self antigen in Lyn‐deficient mice

“…Indirect support comes from the association of B cell hyperactivity and intrinsic changes in B cell function with disease susceptibility loci in mouse models of spontaneous systemic lupus erythematosus (SLE) such as NZB and NZBÂNZW mice [9][10][11][12][13]. B cell hyperactivity is also well documented in SLE patients, who can present with polyclonal B cell activation and high titres of antibodies specific to chemical haptens and foreign antigens, without prior exposure to these antigens [14,15]. However, SLE remains a complex and heterogenous disease [9] and it is not clear to what extent the generation of these antibodies is antigen-independent or induced by crossreacting antigens.…”

Induction of excessive B cell proliferation and differentiation by an in vitro stimulus in culture in human systemic lupus erythematosus.

“…The B cell hyperactivity associated with SLE is actually detectable via almost any measure of B cell function: peripheral blood B cells from patients with SLE have significantly greater proliferation than did control B cells (1,2); patients with SLE have markedly increased numbers of spontaneous immunoglobulin (Ig)-secreting cells in their blood as determined by reverse hemolytic plaque-forming cell (PFC)' assay (1,(3)(4)(5)(6)(7); SLE patients have increased numbers of B cell colonies generated by peripheral blood non-T cells (2,8); and in-A preliminary report of this work was presented at the 72nd Annual Meeting, Federatipn of American Societies for Experimental Biology, 5 May 1988. creased numbers of B cells expressing unique activated B cell antigens, Ba antigens, on the surface are detected in the blood of SLE patients (1). Nonetheless, it is difficult to demonstrate that B cells of SLE patients excessively respond to in vitro stimuli in culture.…”