To define better the molecular basis for follicular dendritic cell (FDC) function, we used PCR-based cDNA subtraction to identify genes specifically expressed in primary FDC isolated from human tonsils. In this work we report the discovery of a novel gene encoding a small secreted protein, which we term FDC-SP (FDC secreted protein). The FDC-SP gene lies on chromosome 4q13 adjacent to clusters of proline-rich salivary peptides and C-X-C chemokines. Human and mouse FDC-SP proteins are structurally unique and contain a conserved N-terminal charged region adjacent to the leader peptide. FDC-SP has a very restricted tissue distribution and is expressed by activated FDCs from tonsils and TNF-α-activated FDC-like cell lines, but not by B cell lines, primary germinal center B cells, or anti-CD40 plus IL-4-activated B cells. Strikingly, FDC-SP is highly expressed in germinal center light zone, a pattern consistent with expression by FDC. In addition, FDC-SP is expressed in leukocyte-infiltrated tonsil crypts and by LPS- or Staphylococcus aureus Cowan strain 1-activated leukocytes, suggesting that FDC-SP can also be produced in response to innate immunity signals. We provide evidence that FDC-SP is posttranslationally modified and secreted and can bind to the surface of B lymphoma cells, but not T lymphoma cells, consistent with a function as a secreted mediator acting upon B cells. Furthermore, we find that binding of FDC-SP to primary human B cells is markedly enhanced upon activation with the T-dependent activation signals such as anti-CD40 plus IL-4. Together our data identify FDC-SP as a unique secreted peptide with a distinctive expression pattern within the immune system and the ability to specifically bind to activated B cells.
Little is presently known about the specific routes of transmission of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8). To investigate whether this agent might be transmitted vertically from mother to infant, we conducted a study on 89 KSHV seropositive mothers and their newborn infants. Thirteen mothers (14.6%) had KSHV DNA detected in their peripheral blood mononuclear cells (PBMC). Two of 89 samples drawn at birth from infants born to KSHV seropositive mothers had KSHV DNA detectable within their PBMC. These findings suggest that KSHV can be transmitted perinatally, but infrequently. Other routes of transmission such as horizontal transmission remain the most likely means of KSHV transmission. © 2001 Wiley-Liss, Inc. Key words: KSHV; HHV-8; vertical transmissionKaposi's sarcoma-associated herpesvirus is a recently isolated gamma herpesvirus 1 that has been found in all forms of Kaposi Sarcoma (KS), 2 and is now thought to play an important role in the development of this tumor. 3 Current knowledge about the routes of transmission of KSHV is limited. Serological evidence has suggested that there may be several routes of KSHV transmission, including sexual contact, as well as nonsexual contact via saliva. 4 -7 In Africa, cross-sectional serological studies of children in different age groups have shown that infection with KSHV begins during early childhood and its frequency increases with age. 8 -12 This suggests that non-sexual modes of transmission of the virus may be occurring in Africa. The role of vertical transmission of this virus remains poorly understood. Some studies have reported serological data disputing the occurrence of vertical transmission of KSHV 13,14 whereas others have presented contrasting serological data suggesting that vertical transmission does occur. 15,16 A case report of KS in a 6-day-old child 17 strongly suggests that KSHV may indeed be transmitted from a mother to her infant in utero. In our study, we present evidence showing that KSHV can be transmitted vertically from mother to infant. MATERIAL AND METHODS Patient recruitmentA subgroup of 89 KSHV seropositive women and their infants were selected from a cohort of over 2,000 mothers participating in a prospective study at the University Teaching Hospital (UTH) in Lusaka, Zambia. In this cohort, pregnant women in the early stages of labor were recruited for the study at the time of admission to the labor ward of the University Teaching Hospital (UTH), Lusaka, Zambia. Women who were in active labor or who had more than 5 cm cervical dilation were not recruited. Before giving written consent to participate in the study, the women were informed about the purpose of the study and counseled on HIV and KSHV. All women were enrolled before giving birth and their newborns were enrolled immediately after delivery. In case of a multiple delivery, only the first sibling was enrolled into the study. Sample collectionMaternal and infant blood was collected by venipuncture into acid citrate dextrose tubes and ...
Little is presently known about the specific routes of transmission of Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus-8 (HHV-8). To investigate whether this agent might be transmitted vertically from mother to infant, we conducted a study on 89 KSHV seropositive mothers and their newborn infants. Thirteen mothers (14.6%) had KSHV DNA detected in their peripheral blood mononuclear cells (PBMC). Two of 89 samples drawn at birth from infants born to KSHV seropositive mothers had KSHV DNA detectable within their PBMC. These findings suggest that KSHV can be transmitted perinatally, but infrequently. Other routes of transmission such as horizontal transmission remain the most likely means of KSHV transmission. © 2001 Wiley-Liss, Inc. Key words: KSHV; HHV-8; vertical transmissionKaposi's sarcoma-associated herpesvirus is a recently isolated gamma herpesvirus 1 that has been found in all forms of Kaposi Sarcoma (KS), 2 and is now thought to play an important role in the development of this tumor. 3 Current knowledge about the routes of transmission of KSHV is limited. Serological evidence has suggested that there may be several routes of KSHV transmission, including sexual contact, as well as nonsexual contact via saliva. 4 -7 In Africa, cross-sectional serological studies of children in different age groups have shown that infection with KSHV begins during early childhood and its frequency increases with age. 8 -12 This suggests that non-sexual modes of transmission of the virus may be occurring in Africa. The role of vertical transmission of this virus remains poorly understood. Some studies have reported serological data disputing the occurrence of vertical transmission of KSHV 13,14 whereas others have presented contrasting serological data suggesting that vertical transmission does occur. 15,16 A case report of KS in a 6-day-old child 17 strongly suggests that KSHV may indeed be transmitted from a mother to her infant in utero. In our study, we present evidence showing that KSHV can be transmitted vertically from mother to infant. MATERIAL AND METHODS Patient recruitmentA subgroup of 89 KSHV seropositive women and their infants were selected from a cohort of over 2,000 mothers participating in a prospective study at the University Teaching Hospital (UTH) in Lusaka, Zambia. In this cohort, pregnant women in the early stages of labor were recruited for the study at the time of admission to the labor ward of the University Teaching Hospital (UTH), Lusaka, Zambia. Women who were in active labor or who had more than 5 cm cervical dilation were not recruited. Before giving written consent to participate in the study, the women were informed about the purpose of the study and counseled on HIV and KSHV. All women were enrolled before giving birth and their newborns were enrolled immediately after delivery. In case of a multiple delivery, only the first sibling was enrolled into the study. Sample collectionMaternal and infant blood was collected by venipuncture into acid citrate dextrose tubes and ...
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