Contributions of each of the BAFF receptors to the lymphocyte profiles in C57BL/6 mice

IF 4.9 3区 医学 Q2 IMMUNOLOGY Immunology Pub Date : 2024-08-31 DOI:10.1111/imm.13856
William Stohl, Ying Wu, Malka Stohl
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Abstract

BAFF, a vital B cell survival and differentiation factor, has three receptors: B-cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI) and BR3. Although B cells are greatly reduced in B6.Baff−/− (which harbour no BAFF) and B6.Br3−/− mice (which harbour supra-normal levels of BAFF), the distributions of B cell subsets and relationships between Foxp3+ and CD4+ cells in these mice differ. Using a large panel of B6 congenic knockout and/or transgenic mice, we demonstrate that (1) supra-normal levels of BAFF per se do not explain the phenotypic differences between B6.Baff−/− and B6.Br3−/− mice; (2) B cells are expanded in B6.Taci−/− mice, with preferential expansion of follicular (FO) B cells at the expense of CD19+CD21−/loCD23−/lo B cells but without the preferential expansion of Foxp3+ cells observed in B6 mice bearing a Baff transgene; (3) despite no expansion in total B cells, percentages of FO B cells and marginal zone B cells are higher and percentages of CD19+CD21−/loCD23−/lo B cells are lower in young B6.Bcma−/− mice, consistent with the inability of B6.Br3−/−.Taci−/− mice to recapitulate the B cell profile of B6.Baff−/− mice; and (4) percentages of Foxp3+ cells in B6.Br3−/−.Taci−/− mice are intermediate between those in B6.Br3−/− and B6.Taci−/− mice despite the B cell profile of B6.Br3−/−.Taci−/− mice strongly resembling that of B6.Br3−/− mice. Collectively, our findings point to a non-redundant role for each of the BAFF receptors in determining the ultimate lymphocyte profile of the host. This may have clinically relevant ramifications in that the degree that a candidate therapeutic agent blocks engagement of any given individual BAFF receptor may affect its clinical utility.

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每种 BAFF 受体对 C57BL/6 小鼠淋巴细胞特征的贡献。
BAFF 是一种重要的 B 细胞存活和分化因子,有三种受体:B 细胞成熟抗原(BCMA)、跨膜激活剂和 CAML 间体(TACI)以及 BR3。虽然B6.Baff-/-小鼠(不携带BAFF)和B6.Br3-/-小鼠(携带超正常水平的BAFF)体内的B细胞大大减少,但这些小鼠体内B细胞亚群的分布以及Foxp3+细胞和CD4+细胞之间的关系却各不相同。通过使用大量 B6 先天性基因敲除和/或转基因小鼠,我们证明:(1) BAFF 水平超常本身并不能解释 B6.Baff-/- 和 B6.Br3-/- 小鼠之间的表型差异;(2) B 细胞在 B6.Baff-/- 和 B6.Br3-/- 小鼠中扩增。Taci-/-小鼠的B细胞扩增,以牺牲CD19+CD21-/loCD23-/lo B细胞为代价,优先扩增滤泡(FO)B细胞,但在携带Baff转基因的B6小鼠中没有观察到Foxp3+细胞的优先扩增;(3)尽管B细胞总数没有扩增,但在幼年B6.Bcma-/-小鼠中,FO B细胞和边缘区B细胞的百分比较高,CD19+CD21-/loCD23-/lo B细胞的百分比较低。Bcma-/- 小鼠中,与 B6.Br3-/-.Taci-/- 小鼠无法再现 B6.Baff-/- 小鼠的 B 细胞特征相一致;以及(4)B6.Br3-/-.Taci-/- 小鼠中 Foxp3+ 细胞的百分比与 B6.Br3-/-.Taci-/- 小鼠中 Foxp3+ 细胞的百分比相一致。Taci/-小鼠的 Foxp3+ 细胞百分比介于 B6.Br3-/- 和 B6.Taci-/- 小鼠之间,尽管 B6.Br3-/-.Taci-/- 小鼠的 B 细胞图谱与 B6.Br3-/- 小鼠非常相似。总之,我们的研究结果表明,每种 BAFF 受体在决定宿主最终淋巴细胞特征方面都扮演着非多余的角色。这可能会对临床产生影响,因为候选治疗药物阻断任何特定单个 BAFF 受体参与的程度可能会影响其临床效用。
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来源期刊
Immunology
Immunology 医学-免疫学
CiteScore
11.90
自引率
1.60%
发文量
175
审稿时长
4-8 weeks
期刊介绍: Immunology is one of the longest-established immunology journals and is recognised as one of the leading journals in its field. We have global representation in authors, editors and reviewers. Immunology publishes papers describing original findings in all areas of cellular and molecular immunology. High-quality original articles describing mechanistic insights into fundamental aspects of the immune system are welcome. Topics of interest to the journal include: immune cell development, cancer immunology, systems immunology/omics and informatics, inflammation, immunometabolism, immunology of infection, microbiota and immunity, mucosal immunology, and neuroimmunology. The journal also publishes commissioned review articles on subjects of topical interest to immunologists, and commissions in-depth review series: themed sets of review articles which take a 360° view of select topics at the heart of immunological research.
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