Detection of pre - malignant B-1 cells in NZB mice with a restricted CDR3 / DFL 16 region

ABSTRACT

The relationship between the immunoglobulin [Ig] nucleotide sequence and the ability of a B cell to develop into a malignant cell was studied in a subset of B cells, B-l cells. B-l cells become malignant in chronic lymphocytic leukemia [CLL] and are responsible for the production of "natural autoantibodies". The autoimmune NZB mouse has been known as a human malignancy and CLL model, because of the age-dependent onset of clonally expanded hyperdiploid B-l cells in these mice. The Ig heavy chain variable region in hyperdiploid B-1 clones from several NZB mice showed common characteristics in the CDR3 shared with fetal B cells lack of N base insertions and presence of homology sequences at the VH -D-JH junctions that can be encoded by either of the two joined gene segments. Using a degenerative oligoprimer was shown no significant differences in expression of the restricted CDR3/DFL16 region in newborns or in the liver of either strain of mice as young adults. However, the expression of the restricted CDR3/DFL16 in the spleens of young adult NZB was remarkably elevated and showed significant differences from the expression in newborn NZB as well as from young adult and newborn BALB/c mice. It appears that malignant hyperdiploid B-1 cells are derived from fetal B cells. This technique can be used as a molecular marker to demonstrate a relative increase in the expression of this CDR3 in animals pre-destined to develop B-malignancies