Expression of immunoglobulin receptors with distinctive features indicating antigen selection by marginal zone B cells from human spleen

Monica Colombo, Giovanna Cutrona, Daniele Reverberi, Silvia Bruno, Fabio Ghiotto, Claudya Tenca, Kostas Stamatopoulos, Anastasia Hadzidimitriou, Jenny Ceccarelli, Sandra Salvi, Simona Boccardo, Maria Grazia Calevo, Amleto De Santanna, Mauro Truini, Franco Fais, Manlio Ferrarini

Research output: Contribution to journalArticlepeer-review

Abstract

Marginal zone (MZ) B cells, identified as surface (s)IgMhighsIgDlowCD23low/-CD21+CD38- B cells, were purified from human spleens, and the features of their V(D)J gene rearrangements were investigated and compared with those of germinal center (GC), follicular mantle (FM) and switched memory (SM) B cells. Most MZ B cells were CD27+ and exhibited somatic hypermutations (SHM), although to a lower extent than SM B cells. Moreover, among MZ B-cell rearrangements, recurrent sequences were observed, some of which displayed intraclonal diversification. The same diversifying sequences were detected in very low numbers in GC and FM B cells and only when a highly sensitive, gene-specific polymerase chain reaction was used. This result indicates that MZ B cells could expand and diversify in situ and also suggested the presence of a number of activation-induced cytidine deaminase (AID)-expressing B cells in the MZ. The notion of antigen-driven expansion/selection in situ is further supported by the VH CDR3 features of MZ B cells with highly conserved amino acids at specific positions and by the finding of shared ("stereotyped") sequences in two different spleens. Collectively, the data are consistent with the notion that MZ B cells are a special subset selected by in situ antigenic stimuli.

Original languageEnglish
Pages (from-to)294-302
Number of pages9
JournalMolecular medicine (Cambridge, Mass.)
Volume19
Issue number1
DOIs
Publication statusPublished - 2013

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

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