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Heterogeneity of tonsillar subepithelial B lymphocytes, the splenic marginal zone equivalents

M Dono1, S Zupo, N Leanza

  • 1Servizio di Immunologia Clinica and Servizio di Citometria Centro Biotechnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, IST, Genova, Italy. mdono@hp380.ist.unige.it

Journal of Immunology (Baltimore, Md. : 1950)
|May 23, 2000
PubMed

Insights

Subepithelial B cells in human tonsils are diverse. Some have mutated VH4 genes indicating antigen experience, while others possess unmutated VH4 genes, representing virgin or antigen-driven cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Human B cell subsets

Background:

  • Subepithelial (SE) B cells in human tonsils play a crucial role in mucosal immunity.
  • Understanding the heterogeneity of SE B cells, particularly their immunoglobulin variable (VH) gene usage and mutation status, is key to elucidating immune responses at mucosal surfaces.

Purpose of the Study:

  • To investigate the VH4 gene repertoire and mutation status in different subsets of resting and activated SE B cells from human tonsils.
  • To characterize the relationship between VH4 gene mutations, B cell surface markers (IgD, CD27), and cellular expansion in SE B cells.

Main Methods:

  • Analysis of VH4 gene sequences from resting and in vivo-activated SE B cells.
  • Subdivision of resting SE B cells based on IgD and CD27 expression.
  • Assessment of VH4 gene mutation status and identification of identical sequences within molecular clones.

Main Results:

  • Resting SE B cells showed heterogeneity: IgDlow cells had mutated VH4 genes (13/29 clones), while IgM-only cells had predominantly unmutated VH4 genes (25/26 clones).
  • Mutated VH4 genes were mainly found in the CD27high fraction of IgDlow SE B cells, suggesting antigen experience.
  • Identical unmutated VH4DJH sequences in resting IgM-only SE B cells indicated local cellular expansion. Activated SE B cells showed both unmutated and mutated VH4 genes in mu transcripts, and extensive mutations in gamma transcripts.

Conclusions:

  • SE B cells are heterogeneous, comprising antigen-experienced B cells with mutated VH4 genes and a subset with unmutated VH4 genes.
  • The unmutated VH4 gene subset likely includes virgin B cells or cells responding to antigens without significant V gene mutation selection.
  • These findings highlight distinct functional states within the SE B cell population of human tonsils.

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