Autoreactive marginal zone B cells are spontaneously activated but lymph node B cells require T cell help

Academic Article


  • In K/BxN mice, arthritis is induced by autoantibodies against glucose-6-phosphate-isomerase (GPI). To investigate B cell tolerance to GPI in nonautoimmune mice, we increased the GPI-reactive B cell frequency using a low affinity anti-GPI H chain transgene. Surprisingly, anti-GPI B cells were not tolerant to this ubiquitously expressed and circulating autoantigen. Instead, they were found in two functionally distinct compartments: an activated population in the splenic marginal zone (MZ) and an antigenically ignorant one in the recirculating follicular/lymph node (LN) pool. This difference in activation was due to increased autoantigen availability in the MZ. Importantly, the LN anti-GPI B cells remained functionally competent and could be induced to secrete autoantibodies in response to cognate T cell help in vitro and in vivo. Therefore, our study of low affinity autoreactive B cells reveals two distinct but potentially concurrent mechanisms for their activation, of which one is T cell dependent and the other is T cell independent. JEM © The Rockefeller University Press.
  • Authors

    Published In

    Digital Object Identifier (doi)

    Author List

  • Mandik-Nayak L; Racz J; Sleckman BP; Allen PM
  • Start Page

  • 1985
  • End Page

  • 1998
  • Volume

  • 203
  • Issue

  • 8