TY - JOUR
T1 - Expression of immunoglobulin receptors with distinctive features indicating antigen selection by marginal zone B cells from human spleen
AU - Colombo, Monica
AU - Cutrona, Giovanna
AU - Reverberi, Daniele
AU - Bruno, Silvia
AU - Ghiotto, Fabio
AU - Tenca, Claudya
AU - Stamatopoulos, Kostas
AU - Hadzidimitriou, Anastasia
AU - Ceccarelli, Jenny
AU - Salvi, Sandra
AU - Boccardo, Simona
AU - Calevo, Maria Grazia
AU - De Santanna, Amleto
AU - Truini, Mauro
AU - Fais, Franco
AU - Ferrarini, Manlio
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.2119/molmed.2013.00069
DO - 10.2119/molmed.2013.00069
M3 - Article
C2 - 23877718
AN - SCOPUS:84884263840
VL - 19
SP - 294
EP - 302
JO - Molecular Medicine
JF - Molecular Medicine
SN - 1076-1551
IS - 1
ER -