Studies in our laboratory of very low birth weight (VLBW) premature infants (less than 1500 grams) have suggested that the post-natal changes in immune function during the first six months of life reflect an ontogenetic process paralleling the development of the immune system in full term infants during the last trimester of pregnancy. It is also well known that infants and young children exhibit poort immune responses to bacterial polysaccharide antigens. However, the molecular and cellular basis for the delay in responsiveness to this group of antigens, and the developmental processes in the maturation of the immune system in infants is not well understood. The objective of this grant proposal is to determine whether there is an ordered, selective utilization immunoglobulins (Ig), heavy chain (VH) and/or light chain (VK) variable region gene family(ies) during B-cell development in VLBW infants. EBV-transformed peripheral blood B-cells from VLBW infants will be studied for their preferential utilization of different VH and (VK) gene families during Ig gene rearrangement from birth to 10 months of age. Total cellular RNA will be analyzed for the distribution of transcribed MRNA and VH and VK families by Northern blot hybridization with VH and VK gene subgroup probes. The distribution in the expression of these VH and/or VK families by B-cell clones derived from infants of different gestational age and during the first 10 months of life will be studied. Since bacterial polysaccharide antigens are the last group of antigens to which infants and young children are able to make specific antibody, we will examine the utilization of VH and VK gene families in EBV-transformed B-cell lines secreting antibodies to pneumococcal polysaccharide and tetanus toxoid antigens. These findings will be correlated with the repertoire of VH and VK gene subgroup expression in B-cells of VLBW infants during the first year of life. Selective utilization of certain VH and/or VK gene families during recombinatorial events in B-cell development may have important implications for the acquisition of immune competence and self-tolerance in man.
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