Neonatal treatment with monoclonal natural antibodies restores a normal pattern of VH gene utilization in the non-obese diabetic mouse.
The utilization of individual VH7183 genes in the autoimmune non-obese diabetic (NOD) mouse and the normal C57BL/6 mouse, both carrying the IgHb haplotype, was investigated. Nucleotide sequence analyses of a large number of VHDJH rearrangements utilizing VH7183 gene segments allowed us to identify 10 individual members of this family in the IgHb 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 VH7183 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 VH7183 gene utilization. Most interestingly, the deviation from the normal pattern of VH7183 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 play an important role in this process.
Department of Cell and Molecular Biology, University of Umeå, Sweden.
A
A
Andersson
B
B
Ekstrand-Hammarström
B
B
Eriksson
C
C
Overmo
D
D
Holmberg
D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000276:immunology; D000911:Antibodies, Monoclonal; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology*; D005787:Gene Frequency / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D000911:Antibodies, Monoclonal; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region