The diversity of rearranged immunoglobulin heavy chain variable region genes in peripheral blood B cells of preterm infants is restricted by short third complementarity-determining regions but not by limited gene segment usage

The immunoglobulin diversity is restricted in fetal liver B cells. This stu dy examined whether peripheral blood B cells of extremely preterm infants s how similar restrictions (overrepresentation of some gene segments, short t hird complementarity-determining regions [CDR3]). DNA of rearranged immunog lobulin heavy chain genes was amplified by polymerase chain reaction, clone d, and sequenced. A total of 417 sequences were analyzed from 6 preterm inf ants (25-28 weeks of gestation), 6 term infants, and 6 adults. Gene segment s from the entire VH and DH gene locus were rearranged in preterm infants, even though the D(H)7-27 segment was overrepresented (17% of rearrangements ) compared to term infants (7%) and adults (2%). CDR3 was shorter in preter m infants (40 +/- 10 nucleotides) than in term infants (44 +/- 12) and adul ts (48 +/- 14) (P < .001) due to shorter N regions. Somatic mutations were exclusively found in term neonates and adults (mutational frequency 0.8% an d 1.8%). We conclude that preterm infants have no limitations in gene segme nt usage, whereas the diversity of CDR3 is restricted throughout gestation. (Blood, 2001;97:1511-1513) (C) 2001 by The American Society of Hematology.