Polyreactive antigen-binding B cells in the peripheral circulation are IgD(+) and B7(-)

Polyreactive antigen-binding B cells in the peripheral circulation are IgD(+) and B7(-)
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DOI:
10.1002/eji.1830261217
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发表时间:
1996-12-01
影响因子:
5.4
通讯作者:
Notkins, AL
Notkins, AL
中科院分区:
医学3区
文献类型:
--
作者:
Chen, ZJ;Shimizu, F;Notkins, AL

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多反应性抗体是自然产生的抗体,主要是IgM同型抗体,能够与各种不同的自身和非自身抗原反应。以前我们曾报道过,能够产生多反应性抗体的B细胞表面有Ig受体,可以与不同的抗原结合。本研究旨在进一步鉴定这些多反应性抗原结合B细胞。一组异硫氰酸荧光素标记的抗原(胰岛素、Ig G-Fe片段或β-半乳糖苷酶)作为探针,通过细胞分选来选择多反应性抗原结合B细胞。我们的实验表明,这些多反应性抗原结合B细胞主要是IGD亚型。它们高水平表达CD40和主要组织相容性复合体II类分子,但很少或不表达B7-1、B7-2或Fas。与抗原与单反应性受体(通常是高亲和力)的结合相反,抗原与多反应性受体(通常是中亲和力或低亲和力)的结合不会上调B7-1或B7-2的表达。然而,与多反应受体结合的抗原被内化和降解,尽管不如与单反应受体结合的抗原有效。尽管这些B7(-)细胞有处理抗原的能力,但它们不能在混合白细胞反应中激活T细胞。结论:多反应性抗原结合B细胞具有诱导免疫耐受的能力。
Polyreactive antibodies are naturally occurring antibodies, primarily of the IgM isotype, that are capable of reacting with a wide variety of different self and nonself antigens. Previously we reported that a B cell capable of making polyreactive antibody has Ig receptors on its surface that can bind different antigens. The present investigation was initiated to characterize these polyreactive antigen-binding B cells further. A panel of fluorescein isothiocyanate-labeled antigens (insulin, IgG Fe fragment or beta-galactosidase) served as probes to select polyreactive antigen-binding B cells by cell sorting. Our experiment revealed that these polyreactive antigen-binding B cells were mainly of the IgD isotype. They expressed high levels of CD40 and major histocompatibility complex class II molecules, but little or no B7-1, B7-2, or Fas. In contrast to the binding of antigens to monoreactive receptors (usually high affinity), the binding of antigens to polyreactive receptors (usually moderate or low affinity) did not up-regulate the expression of B7-1 or B7-2. Antigens that bound to polyreactive receptors, however, were internalized and degraded, although not as efficiently as antigens that bound to monoreactive receptors. Despite the ability of these B7(-) cells to process antigens, they were not able to activate T cells in a mixed leukocyte reaction. It is concluded that polyreactive antigen-binding B cells have properties that are consistent with the ability to induce immunological tolerance.