Maintenance of long term gamma-herpesvirus B cell latency is dependent on CD40-mediated development of memory B cells.
It has been proposed that the gamma-herpesviruses maintain lifelong latency in B cells by gaining entry into the memory B cell pool and taking advantage of host mechanisms for maintaining these cells. We directly tested this hypothesis by kinetically monitoring viral latency in CD40(+) and CD40(-) B cells from CD40(+)CD40(-) mixed bone marrow chimera mice after infection with a murine gamma-herpesvirus, MHV-68. CD40(+) B cells selectively entered germinal centers and differentiated into memory B cells. Importantly, latency was progressively lost in the CD40(-) B cells and preferentially maintained in the long-lived, isotype-switched CD40(+) B cells. These data directly demonstrate viral exploitation of the normal B cell differentiation pathway to maintain latency.
Kim
In-Jeong
IJ
Trudeau Institute, Saranac Lake, NY 12983, USA.
Flaño
Emilio
E
Woodland
David L
DL
Lund
Frances E
FE
Randall
Troy D
TD
Blackman
Marcia A
MA
D016475:3T3 Cells; D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D001854:Bone Marrow Cells / Q000276:immunology / Q000528:radiation effects; D016026:Bone Marrow Transplantation; D019013:CD40 Antigens / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002470:Cell Survival / Q000235:genetics; D018142:Gammaherpesvirinae / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000821:virology; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology*; D017578:Immunoglobulin Class Switching; D007156:Immunologic Memory / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011828:Radiation Chimera; D017735:Virus Latency / Q000235:genetics / Q000276:immunology*
D019013:CD40 Antigens