Stromal cell independent B cell development in vitro: generation and recovery of autoreactive clones.

Journal of Immunological Methods
T Matt HollGarnett Kelsoe

Abstract

We describe and characterize a stromal cell independent culture system that efficiently supports pro-B cell to IgM+ B cell development with near normal levels of IgH and Igkappa diversity. Pro-B cells present in non-adherent bone marrow cells proliferate in the presence of IL-7 and subsequent to the removal of IL-7 and addition of BAFF, differentiate normally into IgM+ B cells. B cell development in vitro closely follows the patterns of development in vivo with culture-derived (CD) B cells demonstrating characteristic patterns of surface antigen expression and gene activation. IgM+ CD B cells respond to TLR stimulation by proliferation and differentiation into antibody-secreting cells. Self-reactive IgM+ B cell development is blocked in 3H9 IgH knockin mice; however, cultures of 3H9 IgH knockin pro-B cells yields high frequencies of "forbidden", autoreactive IgM+ B cells. Furthermore, serum IgG autoantibody exceeded that present in autoimmune, C4(-/-) animals following the reconstitution of RAG1(-/-) mice with IgM+ CD cells derived from BL/6 mice.

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Citations

Jun 28, 2011·Proceedings of the National Academy of Sciences of the United States of America·Masayuki KuraokaGarnett Kelsoe
Apr 29, 2011·Current Opinion in Immunology·Laurent VerkoczyBarton F Haynes
Jun 22, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·N Max SchablaPatrick C Swanson
Mar 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·T Matt HollGarnett Kelsoe
Feb 6, 2019·Nature Immunology·Consuelo AnzilottiSophie Hambleton
May 16, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Matthias PfeiferNiklas Feldhahn
Sep 13, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laurent VerkoczyBarton F Haynes
Apr 25, 2018·Frontiers in Immunology·Sarah A GreavesRoberta Pelanda
Feb 2, 2019·Cellular & Molecular Immunology·Man LiBing Su

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