The contribution of autoantibody-inducing CD4+ T cell (aiCD4 T cell) help to the B cell maturation and possible autoantibody in Systemic Lupus Erythematosus

Abstract

Abstract INTRODUCTION Autoantibody-inducing CD4 T (aiCD4 T) cell seems indispensable for the self-organized criticality theory that induces Systemic Lupus Erythematosus (SLE). We previously found that the aiCD4 T cell belongs to CD45RBlo122lo CD4 T cell subpopulation. We here analyze the B cell population and CD19+ splenic B cell receptor (BCR) repertoire, and test our contention whether aiCD4 T cell helps B cell maturation. METHODS BALB/c mice were immunized with OVA twelve times and SLE was induced. Cell surface markers of B cell were detected with flow cytometry. CD19+ splenic B cells were sorted and BCR repertoires of these cells were analyzed on next generation sequencer. RESULTS After twelve times immunization of mice with OVA, follicular B (Fo B) cell and germinal center B (GC B) cell were significantly increased(P<0.05), whereas marginal zone B cell was decreased. Activation markers of the B cell were increased and in particular, CD80 was significantly increased (P<0.05). In addition, the number of clonotypes of CD19+ splenic B cells in OVA immunized mice was increased. Among these repertoires, the same pairs of V and J usage were frequently found in OVA immunized mice. CONCLUSION Fo B cell and GC B cell and the activation markers of B cell, as well, were significantly increased in OVA immunized mice, and the result of BCR repertoire analysis suggested that somatic hyper mutation occurred frequently in OVA-stimulated mice, which is compatible with the contention that aiCD4 T cells helps the maturation of B cells into germinal center B cells to enhance autoantibody formation thereby inducing SLE.