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Blood, 1 November 2001, Vol. 98, No. 9, pp. 2745-2751
IMMUNOBIOLOGY
Slow, programmed maturation of the immunoglobulin HCDR3
repertoire during the third trimester of fetal life
Harry W. Schroeder Jr,
Liming Zhang, and
Joseph B. Philips III
From the Division of Developmental and Clinical
Immunology, Departments of Medicine and Microbiology, and the Division
of Neonatology, Department of Pediatrics, University of Alabama at
Birmingham.
The mean distribution of lengths in the third
complementarity-determining region of the heavy chain (HCDR3) serves as
a measure of the development of the antibody repertoire during
ontogeny. To determine the timing and pattern of HCDR3 length
maturation during the third trimester of pregnancy, the mean
distribution of HCDR3 lengths among
variable-diversity-joining-constant-µ (VDJCµ) transcripts from the cord blood was analyzed from 138 infants of 23 to
40 weeks' gestation, including 3 sets of twins, 2 of which were of
dizygotic origin. HCDR3 maturation begins at the start
of the third trimester; follows a slow, continuous expansion over a
5-month period; and is unaffected by race or sex. The range and mean
distribution of lengths may vary in dizygotic twins, indicating
individual rates of development. The mean HCDR3 length distribution in
10 premature infants with documented bacterial sepsis was then followed
for 2 to 12 weeks after their first positive blood culture. HCDR3
spectrotype analysis demonstrated oligoclonal B-cell activation and
expansion after sepsis, but maturation of the repertoire was not
accelerated even by the systemic exposure to external antigen
represented by bacteremia. Antibody repertoire development appears to
be endogenously controlled and adheres to an individualized
developmental progression that probably contributes to the relative
immaturity of the neonatal immune response.
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