NEONATAL TREATMENT WITH MONOCLONAL NATURAL ANTIBODIES RESTORES A NORMAL PATTERN OF V-H GENE UTILIZATION IN THE NONOBESE DIABETIC MOUSE

The utilization of individual V(H)7183 genes in the autoimmune non-obese diabetic (NOD) mouse and the normal C57BL/6 mouse, both carrying the IgH(b) haplotype, was investigated. Nucleotide sequence analyses of a large number of V(H)DJ(H) rearrangements utilizing V(H)7183 gene segments allowed us to identify 10 individual members of this family in the IgH(b) haplotype. Eight of these members were isolated from both C57BL/6 and NOD mice, whereas two were found only in NOD mice. Analysis of polymerase chain reaction libraries derived from genomic DNA revealed that >50% of the V(H)7183 rearrangements isolated from both neonatal and adult NOD mice were functional; In contrast, the frequency of functional rearrangements decreased from 61% in neonatal to 9% in adult splenic B cells of C57BL/6 origin. These observations suggested that adult NOD mice retained a neonatal pattern of V(H)7183 gene utilization. Most interestingly, the deviation from the normal pattern of V(H)7183 utilization observed in the adult NOD mouse could be 'normalized' by neonatal treatment with a natural mAb previously demonstrated to inhibit the development of diabetes in the NOD mouse. These data demonstrate that certain 'natural' mAbs can influence the development of T cell mediated autoimmunity in the NOD mouse and suggest that the B cell/Ig compartment may pray an important role in this process.