Salmonella Infection Drives Promiscuous B Cell Activation Followed by Extrafollicular Affinity Maturation

Immunity. 2015 Jul 21;43(1):120-31. doi: 10.1016/j.immuni.2015.06.013. Epub 2015 Jul 14.

Abstract

The B cell response to Salmonella typhimurium (STm) occurs massively at extrafollicular sites, without notable germinal centers (GCs). Little is known in terms of its specificity. To expand the knowledge of antigen targets, we screened plasmablast (PB)-derived monoclonal antibodies (mAbs) for Salmonella specificity, using ELISA, flow cytometry, and antigen microarray. Only a small fraction (0.5%-2%) of the response appeared to be Salmonella-specific. Yet, infection of mice with limited B cell receptor (BCR) repertoires impaired the response, suggesting that BCR specificity was important. We showed, using laser microdissection, that somatic hypermutation (SHM) occurred efficiently at extrafollicular sites leading to affinity maturation that in turn led to detectable STm Ag-binding. These results suggest a revised vision of how clonal selection and affinity maturation operate in response to Salmonella. Clonal selection initially is promiscuous, activating cells with virtually undetectable affinity, yet SHM and selection occur during the extrafollicular response yielding higher affinity, detectable antibodies.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • B-Lymphocytes / immunology*
  • Clonal Selection, Antigen-Mediated / genetics
  • Clonal Selection, Antigen-Mediated / immunology*
  • Germinal Center / immunology*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / immunology
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology
  • Salmonella Infections / immunology
  • Salmonella Infections / microbiology
  • Salmonella typhimurium / immunology*
  • Somatic Hypermutation, Immunoglobulin / genetics
  • Somatic Hypermutation, Immunoglobulin / immunology*
  • Spleen / cytology
  • Spleen / immunology

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Receptors, Antigen, B-Cell