Relationship between immunoglobulin production and immortalization by Epstein Barr virus.
After infection with Epstein Barr virus (EBV), human B lymphocytes actively secrete immunoglobulin (Ig) and are immortalized to become long-term cell lines. In these studies, we investigated the relationship between these virally induced processes utilizing limiting dilution culture techniques, and asked whether all B cells stimulated by EBV to secrete Ig are also immortalized. The activation of B cells by EBV resulting in Ig production and immortalization involved a single precursor cell, required live viral particles, and was independent of immunity to EBV by the lymphocyte donor. However, the precursor frequency of B cells activated to secrete Ig (mean 4.7%) was higher than the precursor frequency of B cells activated to long-term in vitro growth (mean 2.1%). When examined at a single cell level, it appeared that although the vast majority of the immortalized B cells also secrete Ig, only approximately 50% of the B cell precursors induced by EBV to secrete Ig go on to form long-term cell lines. In addition, although immortalized B cell clones producing all major classes of Ig were detected, IgM-committed precursors were more likely to become immortal than were precursors committed to IgG or IgA production. In contrast to these findings in B cells freshly infected with EBV, Ig production was almost always associated with evidence of long-term growth when B cells from previously established EBV-induced B cell lines were tested in identical limiting dilution cultures. Thus, after infection with EBV, human B cells can either become transiently activated to proliferate and to secrete Ig, or become transformed into long-term cell lines most of which produce Ig.
Tosato
G
G
Blaese
R M
RM
Yarchoan
R
R
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002460:Cell Line; D002472:Cell Transformation, Viral; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007126:Immunoglobulin Allotypes / Q000032:analysis / Q000096:biosynthesis; D007136:Immunoglobulins / Q000032:analysis / Q000096:biosynthesis*; D008213:Lymphocyte Activation
D007126:Immunoglobulin Allotypes; D007136:Immunoglobulins