TY - JOUR
T1 - Diversity and somatic hypermutation of the Ig VHDJH, VκJκ, and VλJλ gene segments in lymphoma B cells
T2 - Relevance to the origin of the neoplastic B cell clone
AU - Riboldi, Piersandro
AU - Ikematsu, Wataru
AU - Brambilla, Benedetta
AU - Caprani, Claudia
AU - Gerosa, Maria
AU - Casali, Paolo
N1 - Funding Information:
This work was supported by the USPHS NIH grants AR 40908 and AI 45011 to P.C. and by the AIDS Research Project grant 9306-10 (Rome, Italy) to P.R. We are grateful to Dr. Riccardo Dalla-Favera for his generous donation of many of the cell lines analyzed here. We thank Ms. Shefali Shah for her skillful technical help.
PY - 2003/1/1
Y1 - 2003/1/1
N2 - Burkitt's lymphoma (BL) is a malignancy of B cells characterized by chromosomal translocations involving the immunoglobulin (Ig) and c-MYC gene loci. To address the putative role of antigen in the clonal expansion of these neoplastic B cells, we analyzed the VHDJH and VLJL gene segments expressed by the established cell lines derived from six endemic BL and six sporadic BL. Eight BL cell lines used genes of the VH3 family, two of the VH4, and two of the VH1. Eight VL chains were κ (four members of the Vκ3, two of the Vκ1, and two of the Vκ2 subgroups) and four λ (three members of the Vλ1 and one of the Vλ3 subgroup). The VH gene utilization was stochastic (i.e., it reflected the relative representation of the different VH gene family members in the human haploid genome). In contrast, the VL gene utilization was skewed toward the overutilization of the Vκ3 and Vλ1 gene subgroups. When compared with those of the respective germline genes, the sequences of the expressed Ig V(D)J genes displayed nucleotide differences that resulted from somatic hypermutation. In three endemic and three sporadic BL cells, nucleotide changes yielding amino acid substitutions segregated within the complementarity determining region, indicating the application of a positive pressure for replacement mutations and suggesting that these neoplastic lymphocytes underwent a process of clonal selection driven by antigen, perhaps emerging from or transitioning through germinal centers.
AB - Burkitt's lymphoma (BL) is a malignancy of B cells characterized by chromosomal translocations involving the immunoglobulin (Ig) and c-MYC gene loci. To address the putative role of antigen in the clonal expansion of these neoplastic B cells, we analyzed the VHDJH and VLJL gene segments expressed by the established cell lines derived from six endemic BL and six sporadic BL. Eight BL cell lines used genes of the VH3 family, two of the VH4, and two of the VH1. Eight VL chains were κ (four members of the Vκ3, two of the Vκ1, and two of the Vκ2 subgroups) and four λ (three members of the Vλ1 and one of the Vλ3 subgroup). The VH gene utilization was stochastic (i.e., it reflected the relative representation of the different VH gene family members in the human haploid genome). In contrast, the VL gene utilization was skewed toward the overutilization of the Vκ3 and Vλ1 gene subgroups. When compared with those of the respective germline genes, the sequences of the expressed Ig V(D)J genes displayed nucleotide differences that resulted from somatic hypermutation. In three endemic and three sporadic BL cells, nucleotide changes yielding amino acid substitutions segregated within the complementarity determining region, indicating the application of a positive pressure for replacement mutations and suggesting that these neoplastic lymphocytes underwent a process of clonal selection driven by antigen, perhaps emerging from or transitioning through germinal centers.
KW - B lymphocytes
KW - Burkitt's lymphoma
KW - Somatic mutations
KW - V genes
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U2 - 10.1016/S0198-8859(02)00740-1
DO - 10.1016/S0198-8859(02)00740-1
M3 - Article
C2 - 12507816
AN - SCOPUS:12244267968
SN - 0198-8859
VL - 64
SP - 69
EP - 81
JO - Human Immunology
JF - Human Immunology
IS - 1
ER -