Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection.
Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4(+) T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection.
Zhang
Zhi-Qiang
ZQ
Department of Vaccines and Biologics Research, Merck Research Laboratories, West Point, PA 19486, USA. zhiqiang_zhang@merck.com
Casimiro
Danilo R
DR
Schleif
William A
WA
Chen
Minchun
M
Citron
Michael
M
Davies
Mary-Ellen
ME
Burns
Janine
J
Liang
Xiaoping
X
Fu
Tong-Ming
TM
Handt
Larry
L
Emini
Emilio A
EA
Shiver
John W
JW
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001402:B-Lymphocytes / Q000166:cytology; D001706:Biopsy; D002452:Cell Count; D018450:Disease Progression; D018858:Germinal Center / Q000276:immunology / Q000821:virology; D006965:Hyperplasia / Q000473:pathology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology; D008253:Macaca mulatta; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D019562:Viral Load
D000914:Antibodies, Viral