DISTINCTIVE FEATURES OF IMMUNOGLOBULIN HEAVY-CHAIN VARIABLE REGION GENE REARRANGEMENT IN MULTIPLE-MYELOMA

被引：15

作者：

BAKER, BW ^{[1
]}

DEANE, M ^{[1
]}

GILLEECE, MH ^{[1
]}

JOHNSTON, D ^{[1
]}

SCARFFE, JH ^{[1
]}

NORTON, JD ^{[1
]}

机构：

[1] CHRISTIE HOSP NATL HLTH SERV TRUST,PATERSON INST CANC RES,DEPT GENE REGULAT,CRC,MANCHESTER M20 9BX,ENGLAND

来源：

LEUKEMIA & LYMPHOMA | 1994年 / 14卷 / 3-4期

基金：

英国医学研究理事会;

关键词：

IMMUNOGLOBULIN; HEAVY CHAIN; VARIABLE REGION; GENE REARRANGEMENT; MULTIPLE MYELOMA;

D O I：

10.3109/10428199409049681

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

We have analysed the rearranged Ig heavy chain (IgH) genes in a series of 28 cases of multiple myeloma (MM), in order to extend the study of Ig heavy chain variable (V-H) gene usage in B lymphoid malignancies and to explore the ontogenic compartment from which transformed precursor cells arise in this disease. We were able to amplify 28 rearranged alleles by polymerase chain reaction from 23 of these cases, using a common joining region (J(H)) amplimer together with a panel of V-H family-specific amplimers. The pattern of V-H family usage was similar to that reported in normal peripheral blood B cells with infrequent usage of V(H)5 and V(H)6 genes. However, nucleotide sequence analysis of 17 IgH alleles revealed rearrangement of other V-H family members, closely related to known developmentally regulated V-H genes, some of which are known to be associated with autoimmune specificities. In contrast to previous findings on more immature B lineage malignancies, the rearranged genes diverged extensively from consensus germline sequences, consistent with somatic mutation. These findings support the hypothesis that the major proliferating precursor in MM arises at, or following a stage of T cell-dependent germinal centre proliferation in lymphoid follicles.

引用

页码：291 / 301

页数：11

共 39 条

[1]

Barlogie B., Epstein J., Selvanayagam P., Alexanian R., Plasma cell myeloma-new biological insights and advances in therapy, Blood, 73, pp. 865-879, (1989)

[2]

Tonegawa S., Somatic generation of antibody diversity, Nature, 302, pp. 575-581, (1983)

[3]

Berenson J., Wong R., Kim K., Brown N., Lichtenstein A., Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma, Blood, 70, (1987)

[4]

Deane M., Norton J.D., Immunoglobulin heavy chain variable region family usage is independent of tumour cell phenotype in human B lineage leukaemias, Eur. J. Immunol., 20, pp. 2209-2217, (1990)

[5]

Deane M., Norton J.D., Preferential rearrangement of developmentally regulated immunoglobulin VH1 genes in human B lineage leukaemias, Leukemia, 5, pp. 646-650, (1991)

[6]

Logtenberg T., Schutte M.E., Inghirami G., Berman J.E., Gmelig-Meyling F.H.J., Insel R.A., Knowles D.M., Alt F.W., Immunoglobulin VH gene expression in human B cell lines and tumours: biased VH gene expression in chronic lymphocytic leukaemia, Int. Immunol., 1, pp. 362-366, (1989)

[7]

Pascual V., Capra J.D., Human immunoglobulin heavy-chain variable region genes: organization, polymorphism and expression, Adv. Immunol., 49, pp. 1-74, (1991)

[8]

Pratt L.F., Szubin R., Carson D.A., Kipps T.J., Molecular characterization of a supratypic cross-reactive idiotype associated with IgM autoantibodies, J. Immunol., 147, pp. 2041-2046, (1991)

[9]

Inghirami G., Foitl D.R., Sabichi A., Zhu B.Y., Knowles D.M., Autoantibody-associated cross-reactive idiotype-bearing human B Lymphocytes: distribution and characterization, including Ig VH gene and CD5 antigen expression, Blood, 78, pp. 1503-1515, (1991)

[10]

Casali P., Notkins A.L., Probing the human B-cell repertoire with EBV: polyreactive antibodies and CD5 + B lymphocytes, Annu. Rev. Immunol., 7, pp. 513-535, (1989)

← 1 2 3 4 →