Abstract
The published antibodies (Abs) against CD22 on B cells including Epratuzumab could inhibit B cell activation mainly through binding to C2-set Ig domain of CD22, but they are rarely reported to modulate the pathogenic CD4+ T cell function in systemic lupus erythematosus (SLE). Recently, it was proved that the extracellular amino-terminal V-set Ig domain of CD22 might mediate the interaction of B and T cells, but for now the exact effect of this domain on CD4+ T cell biology have not been identified. Thus, in this study, we screened out a peptide termed B2285 from this V-set Ig domain, developed the novel specific anti-B2285 Abs in rabbits, and investigated their effects in MRL/lpr mice with spontaneous SLE. The results showed that anti-B2285 Abs could ameliorate the disease severity obviously in spontaneous SLE mice with the decreased differentiations of Th1 and Th17 cells and no changes of Th2 and Treg cells. In co-cultured B cells and CD4+ T cells, this specific anti-CD22 Abs was observed to inhibit the anti-dsDNA Abs production, CD4+ T cells proliferation, the protein levels of T-bet and RORγt, and the mRNA levels of TNF-α, IFN-γ, IL-6 and IL-17 in CD4+ T cells. Moreover, the expression of CD45RO on CD4+ T cells could be also apparently diminished by this novel Abs. The data suggested that anti-B2285 Abs could slow SLE progression significantly by regulating Th1 and Th17 cells function via B-T cell interaction and the cytokine network regulation. The treatment against V-set Ig domain of CD22 would be a valuable therapeutic method for SLE and other autoimmune diseases.
Highlights
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with growing morbidity, increasing mortality, and poor life quality [1]
Selection for CD22 peptides in V-set Ig domains Mouse CD22 contains 868 amino acids, and the continuous 109 amino acids from 26th to 134th are localized on V-set Ig domain (GenBank: AAD30391.1)
Only anti-B2285 Abs could recognize and bind to CD22 protein extracted from B cells (Fig. 2B)
Summary
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with growing morbidity, increasing mortality, and poor life quality [1]. It is characterized by autoantibodies production, immune complex deposition, and subsequent multiple organ injury. B cells are generally thought to promote SLE development by producing pathogenic autoantibodies, and immunotherapy targeting B cells is considered as an attractive treatment for SLE, such as therapeutic antibodies (Abs) against CD20 and CD22. There are just a few anti-CD22 Abs were developed and published because the function of those CD22 domains had not been completely clarified. It was rarely reported that those pre-existing anti-CD22 Abs could modulate the function of CD4+ T cells which were critical in the pathogenesis of SLE [6]. The more valuable targets need to be developed in lupus
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