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[Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].
1Dept. of Laboratory Medicine and Clinical Sciences, Kyoto University, School of Medicine, Japan.
Gan to Kagaku Ryoho. Cancer & Chemotherapy
|July 1, 1990
Summary
Embryonic B lymphocytes express unmutated immunoglobulin genes, enabling reactivity to self-carbohydrate antigens. This interaction may initiate an early immune network in embryos.
Area of Science:
- Immunology
- Developmental Biology
- Genetics
Background:
- Embryonic development involves specific carbohydrate antigens like SSEA-1, SSEA-3, and SSEA-4.
- The variable region heavy (VH) genes encode antibody binding specificity.
Purpose of the Study:
- To investigate the immunoglobulin gene origins of monoclonal antibodies targeting embryonic carbohydrate antigens.
- To explore the role of germline VH genes in early B cell reactivity and immune network formation.
Main Methods:
- Comparative analysis of nucleic acid sequences of antibody mRNAs and germline VH genes.
- Investigation of VH gene families (X24, VH7183, Q52) in monoclonal antibodies against onco-developmental carbohydrate antigens.
- Analysis of anti-idiotypic antibodies to understand immune network development.
Main Results:
- Antibodies to embryonic carbohydrate antigens predominantly utilize VH genes from the 3'-end families (X24, VH7183, Q52).
- These utilized VH genes show minimal or no somatic mutation from the germline, suggesting direct expression of unmutated genes.
- VH regions of anti-idiotypic antibodies also favored these 3'-end VH families.
Conclusions:
- Unmutated germline VH genes in embryonic B cells can confer reactivity to self-carbohydrate antigens.
- This reactivity may trigger an embryonic immune idiotype network involving self-antigens.
- The findings suggest a role for intrinsic genetic programs in shaping the early immune system.