The Journal of Immunology, Vol 147, Issue 12 4343-4350, Copyright © 1991 by American Association of Immunologists

ARTICLES

Predominance of the prototypic T15 anti-phosphorylcholine junctional sequence in neonatal pre-B cells

AJ Feeney
Division of Immunology, Medical Biology Institute, La Jolla, CA 92037.

The primary antibody response to phosphorylcholine (PC) is dominated by T15 antibodies. There are three families of anti-PC antibodies which can be made in mice: T15, 511, and 603. All use the same H chain V, D, and J segments, but each anti-PC family has a different L chain, as well as a family-specific Vh-D junctional sequence. Here we test the hypothesis that T15 antibodies are dominant because the prototypic T15 V-D junction is generated in pre-B cells more often than the alternative non-T15 V-D junctional sequences. Rearranged IgH genes from DNA derived from fetal or newborn liver pre-B cells and from adult bone marrow pre-B cells of BALB/c mice were amplified by polymerase chain reaction, cloned, and sequenced. DNA from adult splenic B cells was also amplified, for comparison. All V1-DFL16.1 and DFL16.1-Jh1 junctional sequences were analyzed. Fifty-three percent (9/17) of all neonatal pre-B cell V-D junctions with V1 and DFL16.1 had the prototypic T15 junctional sequence, which has no N regions. In contrast, no prototypic T15 V-D junctions were observed in adult pre-B cells, and each junctional sequence was unique. Adult splenic B cells contained an intermediate number of T15-type V-D junctional sequences (7/21). The prototypic D-J junctional sequence used in many anti-PC antibodies was also observed in a high percentage of sequences. The high frequency of T15 junctions in the neonatal pre-B cells can be explained by two observations: 1) N regions are absent in neonatal but not adult junctions and 2) in the absence of N regions, joining of V, D, and J segments may be targeted to short regions of sequence homology near the ends of the genes. This mechanism would preferentially give rise to the T15 V-D and D-J junctions. Preservation of the T15 V-D junction in adult splenic B cells is most likely due to antigenic stimulation of long lived precursors, because a high frequency of T15- type D-J junctions are coexpressed with T15 V-D junctions in splenic sequences. These results predict that T15 anti-PC precursors would be made at a very high frequency in the neonate, and at a much lower frequency in the adult. This may explain why the neonatal period is critical in establishing T15 dominance.

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