Extensive loss of human DNA accompanies loss of antibody production in heteromyeloma hybridoma cells.

Several human B-cell hybridomas produced by fusion with the mouse X human partner (SHM-D33), and previously assessed for stability of human monoclonal antibody production, have now been assessed for (1) presence of structural genes coding for human immunoglobulin, (2) amount of human DNA, and (3) the rate of loss of human DNA. We found that the proportion of human DNA in clonal populations derived from parental hybridoma populations was extremely variable. Human DNA content varied from 20% to 50% in antibody-producing hybridoma clones. However, loss of antibody production is accompanied by loss of structural immunoglobulin genes and an accelerated loss of greater than 95% of the human component of the hybridoma DNA. In one hybridoma clone, the measured rate of depletion of cellular human DNA was dramatically increased soon after loss of antibody production. These data suggest that stability of human antibody production in hybridomas is dependent on the ability of hybridomas to retain human DNA, and that there is clonal heterogeneity with respect to this ability within hybridoma populations.