MONOCLONAL GAMMOPATHIES IN AGING MU,X-TRANSGENIC MICE - INVOLVEMENT OF THE B-1 CELL LINEAGE

Monoclonal gammopathies (MG) are monoclonal proliferative disorders of B cells at the differentiation stage of Ig production. They can be de tected in the serum, either as transient or as persistent homogenous i mmunoglobulin (H-Ig) components. The exact phenotype, localization, an d cell lineage origin of the precursor tells of MG are unknown, but ma y be crucial for both the correct diagnosis and for timely efficient t reatment of the malignant forms. We used for the first time transgenic (Tg) mice (Sp6: mu/chi) to study the origin of MG, In the mu, chi Tg mice a small proportion of B cells can still produce endogenous IgM. T hese cells are of B-1 cell origin. The MG in Tg mice showed a later on set and a lower frequency than those in littermate control mice, mainl y due to a four times lower frequency of benign monoclonal gammopathy. The 10% of B-1 cells that were able to produce endogenous Ig led to t he development of MG in a frequency that was half the number of MG fou nd in normal littermates. None of the MG in Tg mice produced an Ig of the Tg origin and therefore it can be concluded that they originated f rom B-1 cells.