Novel role of the Ras cascade in memory B cell response

Immunity. 2005 Aug;23(2):127-38. doi: 10.1016/j.immuni.2005.06.010.

Abstract

Engagement of the B cell antigen receptor (BCR) triggers the Ras cascade, but the biological role of the latter in B cell response is unknown. Here, we report that in T cell-dependent response, the role of the Ras cascade is confined to memory B cells and possibly marginal zone B cells. When Ras-dependent BCR signaling was impaired, the generation of IgG germinal center B cells was unaffected but the recruitment of high-affinity cells into the memory compartment and terminal differentiation were inhibited. Furthermore, inhibition of MEK activity consistently impaired antibody production by IgG memory B cells (but not naïve B cells) in vitro. Notably, this impairment was countered by overexpression of Bcl-2. Thus, our data suggest that upon antigen stimulation, memory B cells are susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated through the Ras cascade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Antigens / immunology
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / physiology
  • Cells, Cultured
  • Female
  • Immunization, Secondary
  • Immunologic Memory / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • ras Proteins / antagonists & inhibitors
  • ras Proteins / deficiency
  • ras Proteins / genetics
  • ras Proteins / physiology*

Substances

  • Antigens
  • Proto-Oncogene Proteins c-bcl-2
  • ras Proteins