diate EBV infection. Further studies are ongoing re- 
garding the role of this domain in EBV infection 
and in signal transduction and receptor trafficking. 
Dr. Holers and his colleagues have also placed 
the CR2 cDNA in a number of recombinant vec- 
tor backgrounds, including retroviral-based back- 
grounds. These are being utilized to transfer CR2 to 
- various cell lines and naive primary cells. The func- 
tions of CR2 will be analyzed in these different cell 
backgrounds. These studies will increase under- 
standing of the host cell restriction of CR2 function 
in regard to EBV infection and C3d binding and 
processing. 
A major promoter region in the CR2 gene has 
been identified. Because CR2 is deveiopmentally 
regulated during B cell ontogeny, an extensive anal- 
ysis of this region should allow further understand- 
ing of the nucleotide sequence motifs, DNA-binding 
proteins, and other regulatory steps of importance 
in expression of genes during B cell ontogeny. 
To analyze further the evolution and function in 
vivo of CR2, the laboratory has recently identified 
and cloned mouse CR2 cDNA and genomic homo- 
logues. Ongoing analysis of these clones has indi- 
cated a high degree of sequence conservation to 
human CR2 in both cDNA and genomic structure. 
Construction of antibody and other probes to the 
protein predicted by this cDNA are ongoing. These 
PUBLICATIONS 
studies will allow a more definitive analysis of the 
evolution of CR2 and the in vivo role of CR2 in the 
immune response. 
II. Human Phagocytic Fibronectin Receptor (VIA- 5). 
Dr. Holers has recently undertaken an analysis of 
VLA-5 expression on human B cells. He has found 
VLA-5 on pre-B cells but not on mature B cells. Ini- 
tial evidence indicates that activation of human B 
cells may result in reexpression of VLA-5 . These re- 
sults may have importance in cellular homing of 
these cells or in adherence to inflammatory sites. 
The laboratory has also analyzed expression of 
VLA-5 on phagocytic cells, using mouse peritoneal 
macrophages as the primary model. The regulation 
of the expression of this receptor by inflammatory 
mediators has been demonstrated. Resting cells are 
VLA-5 low, and activated cells are VLA-5 high. This 
suggests that the regulation of surface expression 
of these receptors is important in either homing of 
cells to inflammatory loci or adherence to these 
sites. 
Dr. Holers is also Assistant Professor of Medicine 
and Pathology at Washington University School of 
Medicine and Assistant Physician at Barnes Hos- 
pital, St. Louis. 
Articles 
Bora, N.S., Lublin, D.M., Kumar, B V , Hockett, R.D., Holers, VM. , and Atkinson, J.P 1989- Structural gene for 
human membrane cofactor protein (MCP) of complement maps to within 100 kb of the 3' end of the 
C3b/C4b receptor gene. J Exp Med 169:597-602. 
Carel, J.-C, Frazier, B., Ley, T.J., and Holers, VM. 1989. Analysis of epitope expression and the functional rep- 
ertoire of recombinant complement receptor 2 (CR2/CD21) in mouse and human ceils. J Immunol 
143:923-930. 
Fujisaku, A., Harley J.B., Frank, M.B., Gruner, B.A., Frazier, B., and Holers, VM. 1989. Genomic organization 
and polymorphisms of the human C3d/Epstein-Barr virus receptor. J Biol Chem 264:2118-2125. 
Holers, VM. 1989. Complement receptors. Year Immunol 4:231-240. 
Holers, VM. , Ruff, T.G. , Parks, D.L., McDonald, J.A., Ballard, L.L., and Brown, E.J. 1989. Molecular cloning of a 
murine fibronectin receptor and its expression during inflammation. Expression of VLA-5 is increased in 
activated peritoneal macrophages in a manner discordant from major histocompatibility complex class II. 
J Exp Med 169:1589-1605. 
Hourcade, D. , Holers, VM. , and Atkinson, J.P 1989. The regulators of complement activation (RCA) gene 
cluster. A^^f/mmMno/ 45:381-416. 
Hourcade, D., Miesner, D.R., Atkinson, J.P, and Holers, VM. 1988. Identification of an alternative poly- 
adenylation site in the human C3b/C4b receptor (complement receptor type 1) transcriptional unit and 
prediction of a secreted form of complement receptor type 1. J Exp Med 168:1255-1270. 
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