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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Holl, TM; Haynes, BF; Kelsoe, G

Published Date

  • March 31, 2010

Published In

Volume / Issue

  • 354 / 1-2

Start / End Page

  • 53 - 67

PubMed ID

  • 20109461

Pubmed Central ID

  • 20109461

Electronic International Standard Serial Number (EISSN)

  • 1872-7905

Digital Object Identifier (DOI)

  • 10.1016/j.jim.2010.01.007

Language

  • eng

Conference Location

  • Netherlands