Clonal expansions of B lymphocytes in old mice.
The effect of age on the diversity of the murine Ig heavy chain repertoire has been studied in unimmunized C57BL/6 mice. We examined the heterogeneity of complementarity-determining region 3 (CDR3) sizes of Ig mRNA of the IgM and IgG isotypes using two VH families, VHJ558 and VHQ52, which together account for approximately 65% of the Ab repertoire. The broad and bell-shaped profiles representing the diversity of the VHJ558 family in the spleen of 2- to 6-mo-old C57BL/6 mice becomes significantly less diverse after 12 mo of age and by 18 mo of age, single CDR3 sizes that dominate the profiles can be observed in the spleens of > 85% of the mice. Readable sequences have been obtained from 40 dominant mRNA CDR3 size species indicating that they represent clonal populations of B lineage. There are no significant homologies among these sequences. Clones of B lymphocytes that express a dominant CDR3 mRNA species can also be found in the bone marrow, the mesenteric lymph nodes, and the thymus of C57BL/6 mice > 18 mo of age. Some clones of B cells can be detected in only one lymphoid compartment; others are found in two or more compartments. The splenic B cell clones in C57BL/6 mice > 18 mo of age are stable for at least 2 mo. The CDR3 mRNA species that dominate the splenic repertoire of Ig mRNA-expressing cells in vivo do not dominate the repertoire of splenic B cells activated in vitro by bacterial LPS, suggesting that they represent a modest population of B cells expressing high levels of Ig mRNA.
LeMaoult
J
J
Division of Geriatrics and Gerontology, Cornell University Medical College, New York 10021, USA.
Delassus
S
S
Dyall
R
R
Nikolić-Zugić
J
J
Kourilsky
P
P
Weksler
M E
ME
D000375:Aging / Q000235:genetics / Q000276:immunology*; D000818:Animals; D000916:Antibody Diversity / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000502:physiology*; D001854:Bone Marrow Cells / Q000276:immunology; D002999:Clone Cells; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000235:genetics; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000032:analysis; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology
D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger