Antigen-specific antibody responses in B-1a and their relationship to natural immunity
- 14 March 2012
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 109 (14), 5382-5387
- https://doi.org/10.1073/pnas.1121631109
Abstract
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.Keywords
This publication has 42 references indexed in Scilit:
- Antigen-specific memory in B-1a and its relationship to natural immunityProceedings of the National Academy of Sciences, 2012
- Antigen-specific B-1a antibodies induced byFrancisella tularensisLPS provide long-term protection againstF. tularensisLVS challengeProceedings of the National Academy of Sciences of the United States of America, 2009
- Dual role for B-1a cells in immunity to influenza virus infectionThe Journal of Experimental Medicine, 2008
- Division and differentiation of natural antibody-producing cells in mouse spleenProceedings of the National Academy of Sciences, 2007
- ANTIGEN-SPECIFIC MEMORY B CELL DEVELOPMENTAnnual Review of Immunology, 2005
- B‐1 cells: the lineage question revisitedImmunological Reviews, 2000
- Defective B cell development and function in Btk-deficient miceImmunity, 1995
- Germinal CentersAnnual Review of Immunology, 1994
- Maturation of the immune response in germinal centersCell, 1991
- Immunochemical and related interactions with dextrans reviewed in terms of improved structural informationMolecular Immunology, 1986