SalmOnella Infection Drives Promiscuous B Cell Activation Followed By Extrafollicular Affinity Maturation

Roberto Di Niro, Seung Joo Lee, Jason A. Vander Heiden, Rebecca A. Elsner, Nikita Trivedi, Jason M. Bannock, Namita T. Gupta, Steven H. Kleinstein, Francois Vigneault, Tamara J. Gilbert, Eric Meffre, Stephen J Mcsorley, Mark J. Shlomchik

Research output: Contribution to journalArticle

78 Scopus citations

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 ofantigen 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.

Original languageEnglish (US)
Pages (from-to)120-131
Number of pages12
JournalImmunity
Volume43
Issue number1
DOIs
StatePublished - Jul 21 2015

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

Cite this

Di Niro, R., Lee, S. J., Vander Heiden, J. A., Elsner, R. A., Trivedi, N., Bannock, J. M., Gupta, N. T., Kleinstein, S. H., Vigneault, F., Gilbert, T. J., Meffre, E., Mcsorley, S. J., & Shlomchik, M. J. (2015). SalmOnella Infection Drives Promiscuous B Cell Activation Followed By Extrafollicular Affinity Maturation. Immunity, 43(1), 120-131. https://doi.org/10.1016/j.immuni.2015.06.013