BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact.
We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.
Scholz
Jean L
JL
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6082, USA.
Crowley
Jenni E
JE
Tomayko
Mary M
MM
Steinel
Natalie
N
O'Neill
Patrick J
PJ
Quinn
William J
WJ
Goenka
Radhika
R
Miller
Juli P
JP
Cho
Yun Hee
YH
Long
Vatana
V
Ward
Chris
C
Migone
Thi-Sau
TS
Shlomchik
Mark J
MJ
Cancro
Michael P
MP
D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D053264:B-Cell Activating Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL
D053264:B-Cell Activating Factor