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Follicular Dendritic Cells Modulate Germinal Center B Cell Diversity through FcγRIIB.
van der Poel, Cees E; Bajic, Goran; Macaulay, Charles W; van den Broek, Theo; Ellson, Christian D; Bouma, Gerben; Victora, Gabriel D; Degn, Søren E; Carroll, Michael C.
Afiliação
  • van der Poel CE; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Bajic G; Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Macaulay CW; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA; Boston University, Boston, MA 02215, USA.
  • van den Broek T; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
  • Ellson CD; GSK, Stevenage, Hertfordshire, SG1 2NY, UK.
  • Bouma G; GSK, Stevenage, Hertfordshire, SG1 2NY, UK.
  • Victora GD; The Rockefeller University, New York, NY 10065, USA.
  • Degn SE; Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
  • Carroll MC; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA. Electronic address: michael.carroll@childrens.harvard.edu.
Cell Rep ; 29(9): 2745-2755.e4, 2019 11 26.
Article em En | MEDLINE | ID: mdl-31775042
ABSTRACT
Follicular dendritic cells (FDCs), a rare and enigmatic stromal cell type in the B cell follicles of secondary lymphoid organs, store and present antigen to B cells. While essential for germinal center (GC) responses, their exact role during GC B cell selection remains unknown. FDCs upregulate the inhibitory IgG Fc receptor FcγRIIB during GC formation. We show that the stromal deficiency of FcγRIIB does not affect GC B cell frequencies compared to wild-type mice. However, in the absence of FcγRIIB on FDCs, GCs show aberrant B cell selection during autoreactive and selective foreign antigen responses. These GCs are more diverse as measured by the AidCreERT2 -confetti system and show the persistence of IgM+ clones with decreased numbers of IgH mutations. Our results show that FDCs can modulate GC B cell diversity by the upregulation of FcγRIIB. Permissive clonal selection and subsequent increased GC diversity may affect epitope spreading during autoimmunity and foreign responses.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de IgG / Centro Germinativo / Células Dendríticas Foliculares Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de IgG / Centro Germinativo / Células Dendríticas Foliculares Limite: Animals / Humans Idioma: En Revista: Cell Rep Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos