Antigen-specific antibody responses in B-1a and their relationship to natural immunity

Proc Natl Acad Sci U S A. 2012 Apr 3;109(14):5382-7. doi: 10.1073/pnas.1121631109. Epub 2012 Mar 14.


B-1a cells are primarily thought of as natural antibody-producing cells. However, we now show that appropriate antigenic stimulation induces IgM and IgG B-1a antibody responses and long-lived T-independent antigen-specific B-1a memory that differs markedly from canonical B-2 humoral immunity. Thus, we show here that in the absence of inflammation, priming with glycolipid (FtL) from Francisella tularensis live vaccine strain induces splenic FtL-specific B-1a to mount dominant IgM and activation-induced cytidine deaminase-dependent IgG anti-FtL responses that occur within 3-5 d of FtL priming and fade within 1 wk to natural antibody levels that persist indefinitely in the absence of secondary FtL immunization. Equally surprising, FtL priming elicits long-term FtL-specific B-1a memory cells (IgM>>IgG) that migrate rapidly to the peritoneal cavity and persist there indefinitely, ready to respond to appropriately administrated secondary antigenic stimulation. Unlike B-2 responses, primary FtL-specific B-1a responses and establishment of persistent FtL-specific B-1a memory occur readily in the absence of adjuvants, IL-7, T cells, or germinal center support. However, in another marked departure from the mechanisms controlling B-2 memory responses, rechallenge with FtL in an inflammatory context is required to induce B-1a secondary antibody responses. These findings introduce previously unexplored vaccination strategies for pathogens that target the B-1a repertoire.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Formation*
  • Antigens / immunology*
  • Immunity, Innate*
  • Immunoglobulin G / immunology
  • Immunoglobulin M / immunology
  • Spleen / immunology


  • Antigens
  • Immunoglobulin G
  • Immunoglobulin M