한빛사논문
Sujin Lee 1, Yeunjung Ko 1,3, Hyun Woo Lee 1, Won Joon Oh 1, Hun Gi Hong 1, Dinuka Ariyaratne 2, Se Jin Im 1,* and Tae Jin Kim 1,*
1Department of Immunology, Graduate School of Basic Medical Science, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea.
2Department of Immunology and Molecular Medicine, Faculty of Medical Sciences, University of Sri Jayewardenepura, Nugegoda, Sri Lanka.
3Present address: Immunology and Microbiology Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA.
*Corresponding authors: correspondence to Se Jin Im or Tae Jin Kim
Abstract
Marginal zone (MZ) B cells, which are splenic innate-like B cells that rapidly secrete antibodies (Abs) against blood-borne pathogens, are composed of heterogeneous subpopulations. Here, we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels. CD80high MZ B cells exhibited greater Ab-producing, proliferative, and IL-10-secreting capacities than did CD80low MZ B cells. Notably, CD80high MZ B cells survived 2-Gy whole-body irradiation, whereas CD80low MZ B cells were depleted by irradiation and then repleted with one month after irradiation. Depletion of CD80low MZ B cells led to accelerated development of type II collagen (CII)-induced arthritis upon immunization with bovine CII. CD80high MZ B cells exhibited higher expression of genes involved in proliferation, plasma cell differentiation, and the antioxidant response. CD80high MZ B cells expressed more autoreactive B cell receptors (BCRs) that recognized double-stranded DNA or CII, expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences, and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80low MZ B cells. Adoptive transfer experiments showed that CD21+CD23+ transitional 2 MZ precursors preferentially generated CD80low MZ B cells and that a proportion of CD80low MZ B cells were converted into CD80high MZ B cells; in contrast, CD80high MZ B cells stably remained CD80high MZ B cells. In summary, MZ B cells can be divided into two subpopulations according to their CD80 expression levels, Ab-producing capacity, radioresistance, and autoreactivity, and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.
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