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Evolution of B-cell clonal expansions with age.

Abstract：

:B-cell clonal expansions (BCE) in young mice are transient, detectable for less than 4 weeks. In contrast, BCE in old mice persist more than 2 months. The greater persistence of BCE in old mice does not appear to be due to the age of the host as the survival of phenyloxazolone chicken serum albumin-induced BCE in most old mice was shorter than in young mice. This raises the possibility that persistent BCE seen in old mice develop over time from transient BCE present earlier in life. To test this hypothesis, young C57BL/6 mice were immunized with hen egg lysozyme (HEL) during the first year of life. By 28 months of age, the majority of these mice had developed a benign, persistent BCE associated with a HEL-specific serum mIg. We also investigated whether benign, persistent BCE, present in 18-month-old mice, can evolve into B-cell lymphomas. We observed that four of eight C57BL/6 mice that survived to 29 months of age had developed diffuse large cell lymphomas. In three of these mice, this diagnosis was made by microscopic analysis of the lymphoid organs. In one mouse, a macroscopic lymphoma was present that permitted us to demonstrate that the IgH mRNA CDR3 length and sequence in the malignant lymphoma was derived from a persistent BCE present 11 months earlier. Together these observations are consistent with the hypothesis that stepwise accumulation of genetic alterations combined with Darwinian selection underlies the evolution of B cells from transient BCE in young mice into persistent BCE, serum mIg, and B-cell lymphomas observed in older mice.

journal_name

Cell Immunol

journal_title

Cellular immunology

authors

Szabo P,Li F,Mathew J,Lillvis J,Weksler ME

doi

10.1016/j.cellimm.2005.01.002

subject

Has Abstract

pub_date

2004-09-01 00:00:00

pages

158-67

issue

1-2

eissn

0008-8749

issn

1090-2163

pii

S0008-8749(05)00005-5

journal_volume

231

pub_type

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