Primary Sjögren syndrome specific B cells induced aberrant surface aggregation of B cell receptors (BCRs) and signalling

Abstract

Primary Sjögren’s syndrome (pSS) is a systematic autoimmune manifestation of the exocrine glands caused by impaired lymphocytic infiltration, leading to dry eyes and xerostomia. The pathologic hallmark of this disease is the dysfunction of the exocrine glands, which results in dry eyes and mouth. Clinical observations suggest that B cells contribute to the pathogenesis of pSS through the enhanced secretion of autoantibodies, hypergammaglobulinemia, reduced free light chains, and a higher B cell lymphoma. Despite increased evidence of B cell hyperactivation and dysregulated B cell interactions in pSS, detailed speculations into the mechanism by which pSS-specific B cells exhibited abnormal BCR signaling repertoires and the magnitude of downstream signaling responses remain limited. Upon encountering antigens, B lymphocytes produce neutralizing antibodies by phosphorylating immune receptor tyrosine activation motifs (ITAMs). Despite these advancements, we still do not understand how pSS-specific B cells influence the surface clustering of BCRs and subsequent downstream immune responses. This paper hypothesizes that pSS-specific B cells encountering surrogate antigens will undergo a coordinated series of events that initiate B cell activation and spatiotemporal dynamics of BCRs. Additionally, we assume that pSS individuals have aberrant BCR repertoire and clonal expansion. In the future, these studies can provide detailed therapeutic entanglements for B cell-linked autoimmune and other hypersensitive disorders.