Control of autoreactive B cells by IgM and IgD B cell receptors: maintaining a fine balance

M Noviski, J Zikherman - Current opinion in immunology, 2018 - Elsevier
M Noviski, J Zikherman
Current opinion in immunology, 2018Elsevier
Highlights•IgM, but not IgD, downregulation is a shared feature of autoreactive B cells.•IgD is
less sensitive to endogenous antigens and monovalent antigens than IgM.•IgM and IgD
BCRs may differentially associate with B cell co-receptors.•Autoreactive B cells are
preferentially shunted into the germinal center (GC).•Autoreactive B cells may be
'redeemed'by somatic hypermutation in the GC.A substantial fraction of mature naïve B cells
recognize endogenous antigens, and this autoreactivity must be controlled to prevent …
Highlights
  • IgM, but not IgD, downregulation is a shared feature of autoreactive B cells.
  • IgD is less sensitive to endogenous antigens and monovalent antigens than IgM.
  • IgM and IgD BCRs may differentially associate with B cell co-receptors.
  • Autoreactive B cells are preferentially shunted into the germinal center (GC).
  • Autoreactive B cells may be ‘redeemed’by somatic hypermutation in the GC.
A substantial fraction of mature naïve B cells recognize endogenous antigens, and this autoreactivity must be controlled to prevent autoantibody secretion. Selective downregulation of the IgM BCR on autoreactive B cells has long been appreciated, and recent findings illustrate how this might impose tolerance. The BCR isotype maintained on autoreactive B cells, IgD, is less sensitive to endogenous antigens than IgM. This reduced sensitivity may be conferred by structural properties of IgD and/or differential association with activating and inhibitory co-receptors. Once activated, autoreactive B cells are normally excluded from rapid plasma cell responses, but they can enter the germinal center and lose their autoreactivity through a mutation-selection process termed clonal redemption.
Elsevier