Abstract

The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses. However, the precise molecular mechanisms underlying these selection machineries, including the involvement of antigen receptor signaling molecules, remain to be elucidated. We found that expression levels of Igα and Igβ, which are the essential components of B cell antigen-receptor complex, were differentially regulated in GC B cells and that the expression of Igβ was more prominently down-regulated in a portion of GC B cells. The suppression of Igβ down-regulation reduced the number of GL7+GC B cells and the affinity maturation in T-dependent responses was markedly impaired. In addition, the disease phenotypes in autoimmune-prone mice were ameliorated by blocking of Igβ down-regulation. These results suggest that Igβ down-regulation is involved in the normal positive selection in GC and the accumulation of autoreactive B cells in autoimmune-prone mice.

Highlights

  • The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses

  • According to a previous report[15] and the present data, the expression of Igβ in GC B cells clearly correlated with the down-modulation of IgM. To clarify whether this down-regulation of Igβ in GC B cells reflects the decrease of surface B cell antigen receptor (BCR) expression, we examined the levels of Igβ mRNA following the endocytosis of BCR in vitro (Fig. 1d)

  • We demonstrated quantitatively that the cell surface expression of Igβ was more prominently lowered as compared with that of Igα in the murine GC B cells and that the inhibition of Igβ down-regulation resulted in the impairment of T-dependent immune responses

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Summary

Introduction

The positive and negative selection of antigen-reactive B cells take place in the germinal center (GC) during an immune responses. Igμ chains expressed on the cell surface of B lineage cells in association with Igα /Igβ hetero-dimer play essential roles in both differentiation and survival of preB cells and mature B cells[6,7]. We demonstrated that expression levels of Igα and Igβ , were differentially regulated in GC B cells and that the expression of Igβ was more prominently down-regulated in a part of GC B cells This down-regulation of Igβ is involved both in the effective positive selection in GC B cells and the accumulation of autoreactive B cells in autoimmune-prone mice

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