{"title":"Contributions of each of the BAFF receptors to the lymphocyte profiles in C57BL/6 mice","authors":"William Stohl, Ying Wu, Malka Stohl","doi":"10.1111/imm.13856","DOIUrl":null,"url":null,"abstract":"<p>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.<i>Baff</i><sup>−/−</sup> (which harbour no BAFF) and B6.<i>Br3</i><sup>−/−</sup> mice (which harbour supra-normal levels of BAFF), the distributions of B cell subsets and relationships between Foxp3<sup>+</sup> and CD4<sup>+</sup> 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.<i>Baff</i><sup>−/−</sup> and B6.<i>Br3</i><sup>−/−</sup> mice; (2) B cells are expanded in B6.<i>Taci</i><sup>−/−</sup> mice, with preferential expansion of follicular (FO) B cells at the expense of CD19<sup>+</sup>CD21<sup>−/lo</sup>CD23<sup>−/lo</sup> B cells but without the preferential expansion of Foxp3<sup>+</sup> cells observed in B6 mice bearing a <i>Baff</i> 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<sup>+</sup>CD21<sup>−/lo</sup>CD23<sup>−/lo</sup> B cells are lower in young B6.<i>Bcma</i><sup>−/−</sup> mice, consistent with the inability of B6.<i>Br3</i><sup>−/−</sup><i>.Taci</i><sup>−/−</sup> mice to recapitulate the B cell profile of B6.<i>Baff</i><sup>−/−</sup> mice; and (4) percentages of Foxp3<sup>+</sup> cells in B6.<i>Br3</i><sup>−/−</sup><i>.Taci</i><sup>−/−</sup> mice are intermediate between those in B6.<i>Br3</i><sup>−/−</sup> and B6.<i>Taci</i><sup>−/−</sup> mice despite the B cell profile of B6.<i>Br3</i><sup>−/−</sup><i>.Taci</i><sup>−/−</sup> mice strongly resembling that of B6.<i>Br3</i><sup>−/−</sup> 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.</p>","PeriodicalId":13508,"journal":{"name":"Immunology","volume":null,"pages":null},"PeriodicalIF":4.9000,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/imm.13856","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/imm.13856","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
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.
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.