Possibility of EB virus preferentially transforming a subpopulation of human B lymphocytes

PERMANENT lymphoblastoid cell lines can be established by ‘transformation’ of human lymphocytes with EB virus1,2. The lines secrete immunoglobulin (Ig) in vitro3,4 and represent, morphologically, an intermediate stage between the resting lymphocyte and the fully developed plasma cell5,6. It has been suggested that the EB virus stimulates inactive B lymphocytes to secrete immunoglobulin and that the virus is behaving, in this respect, like a polyclonal B cell mitogen. The evidence comes from observations that most (possibly all) human B lymphocytes carry surface receptors for EB virus8, that an increase in Ig secretion is detectable within a few days of adding the virus to a culture of lymphocytes7, and that in the early stages of growth, lymphoblastoid lines established in this way secrete multiple classes of Ig heavy and light chain4,9,10. It seems, however, that only a fraction of 1% of lymphocytes in an EB virus-infected culture respond either by Ig synthesis or by proliferation and furthermore that the two events occur simultaneously7,11,12. The possibility therefore remains that EB virus does not stimulate Ig synthesis de novo but selectively ‘transforms’ (that is, induces to proliferate) that minor population of B cells which has already begun to secrete Ig. This alternative is supported by our analysis of the major classes of Ig heavy and light chains secreted by lymphoblastoid cell lines (derived from peripheral blood lymphocytes) in relation to the age and clinical status of the donors.