15 SM/J mouse hybridoma antibodies that show antithymocyte autoantibody (ATA) activity by immunofluorescence staining were studied. Half of these antibodies react with determinants whose expression is associated with Thy-1, as shown by blocking experiments with anti-Thy-1 and loss of reactivity with Thy-1- mutant cell lines. The Thy-1 dependence of three of these ATA is further confirmed by their reexpression on a Thy-1 gene transfectant. However, the remaining antibodies exhibited binding that showed little or no dependence on Thy-1. Furthermore, we find that most ATA derives from the Ly-1 B subpopulation, as demonstrated by lipopolysaccharide-induced ATA secretion in vitro and by comparison of ATA hybridoma frequencies. VH region gene sequence data of 14 monoclonal ATA from Ly-1 B cell-derived hybridomas reveal the utilization of nine VH genes belonging to four different VH families (J558, 3609, Q52, and Vgam3.8). While we find that two of these hybridomas arose from a clonal expansion, we also find four examples of a 3609 family VH gene utilized in clonally independent lines showing similar specificity. Yet another example of identical VH gene usage by clonally unrelated cells is found in two J558 ATA of a distinct fine specificity. These data suggest that the enrichment of ATA B cells in the Ly-1 B subset is primarily due to repeated independent recruitment of B cells by antigen resulting in the expression of a restricted set of VH genes.
Article|
September 01 1990
Natural autoantibodies to thymocytes: origin, VH genes, fine specificities, and the role of Thy-1 glycoprotein.
K Hayakawa,
K Hayakawa
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
C E Carmack,
C E Carmack
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
R Hyman,
R Hyman
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
R R Hardy
R R Hardy
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Search for other works by this author on:
K Hayakawa
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
C E Carmack
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
R Hyman
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
R R Hardy
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1990) 172 (3): 869–878.
Citation
K Hayakawa, C E Carmack, R Hyman, R R Hardy; Natural autoantibodies to thymocytes: origin, VH genes, fine specificities, and the role of Thy-1 glycoprotein.. J Exp Med 1 September 1990; 172 (3): 869–878. doi: https://doi.org/10.1084/jem.172.3.869
Download citation file: