that ligand binding to CR2 may play a substantial 
role in the control of specific cellular adhesion 
pathways. These events are likely to figure impor- 
tantly in the various mechanisms by which comple- 
ment regulates the immune response. 
Mouse Homologues of Human Complement 
Receptor and Regulatory Proteins 
Recently Dr. Holers and his colleagues have iden- 
tified three mouse homologues of human RCA pro- 
teins. In these studies the group has determined that 
there are interesting structural differences in the re- 
ceptors and in the mechanism of cell-specific regula- 
tion of expression between the human and mouse 
RCA family members. Despite the differences, how- 
ever, there are very similar, if not identical, func- 
tional activities. 
Each of the three homologues demonstrates this 
point. The first two are products of an alternatively 
spliced mRNA that, in the mouse, encodes the homo- 
logues of two unique human RCA proteins, comple- 
ment receptor 1 (CRl ) and CR2. The third is a novel 
protein, Crry/p65. This protein is a mouse func- 
tional homologue of two human RCA proteins: de- 
cay-accelerating factor and membrane cofactor pro- 
tein. Dr. Holers has demonstrated that Crry/p65 has 
the same biologic activity — control of complement 
deposition on self membranes — as these two human 
proteins. By the construction of appropriate mono- 
clonal and polyclonal reagents, he is characteriz- 
ing in each tissue the cell-specific expression of 
Crry/p65. 
His studies on this protein have suggested that 
within the RCA family an evolutionary switch has 
occurred that has resulted in a mouse protein with 
little structural similarity to decay-accelerating fac- 
tor or membrane cofactor protein but with very simi- 
lar if not identical biologic activities. Ongoing stud- 
ies are characterizing the roles of these proteins in 
the immune response to foreign antigens and in au- 
toimmune disease. 
Regulation of Human CR2 Expression 
Human CR2 is expressed primarily on B lympho- 
cytes in a stage-specific manner. It is not expressed 
on early pre-B cells, is expressed on mature circu- 
lating and germinal center B cells, but is not found 
on immunoglobulin-secreting later-stage B cells or 
plasma cells. Thus CR2 serves as a model of regula- 
tion of stage-specific proteins in this cell type. 
Dr. Holers and his colleagues are currently analyz- 
ing the transcriptional regulatory domains within 
this gene. He has determined that control of surface 
expression is primarily related to transcriptional ac- 
tivation. The laboratory has identified a series of 
functionally important areas within the human CR2 
promoter and a number of transactivating protein 
families involved in this regulation. He is currently 
determining which of these are important in cell- 
and stage-specific expression of CR2. The overall 
goal is to use this information to further an under- 
standing of the molecular genetic mechanisms by 
which B lymphocytes mature and are activated. 
Dr. Holers is also Associate Professor of Medi- 
cine and Assistant Professor of Pathology at Wash- 
ington University School of Medicine and Assis- 
tant Physician at Barnes Hospital, St. Louis. 
Books and Chapters of Books 
Holers, V.M., and Brown, E.J. 1992. Integrins in 
inflammation and the immune response. In Im- 
munology Scope Monograph (Schwartz, B., Ed.). 
Kalamazoo, MI: Upjohn, pp 98-1 10. 
Articles 
Emlen, W., Holers, V.M., Arend, W.P., and Kotzin, 
B. 1992. Regulation of nuclear antigen expres- 
sion on the cell surface of human monocytes. / 
Immunol 148:3042-3048. 
Holers, V.M., Kinoshita, T., and Molina, H. 1992. 
The evolution of mouse and human complement 
C3-binding proteins: divergence of form but con- 
servation of function. Immunol Today 13:231- 
236. 
Hourcade, D., Garcia, A.D., Post, T.W., Taillon- 
Miller, P., Holers, V.M., Wagner, L.M., Bora, 
N.S., and Atkinson, J.P. 1992. Analysis of the 
human regulators of complement activation 
(RCA) gene cluster with yeast artificial chromo- 
somes (YACs). Genomics 12:289-300. 
Krych, M., Atkinson, J.P., and Holers, V.M. 
1992. Complement receptors. Curr Opin Im- 
munol 4:8-1 3. 
Molina, H., Wong, W., Kinoshita, T., Brenner, C, 
Foley, S., and Holers, V.M. 1992. Distinct recep- 
tor and regulatory properties of recombinant 
mouse complement receptor 1 (CRl) and Crry, 
the two genetic homologues of human CRl f Exp 
Med 175:121-129. 
Secrist, H., Holers, V.M., Levine, A., Egan, M., 
Nahm, M.H., Butch, A.W., and Peters, M. 1991. 
Induction of 11-4 and 11-6 synthesis in vitro: varia- 
tion in signaling requirements and kinetics are 
dependent on the anatomic source of the re- 
sponding mononuclear cells. Reg Immunol 
3:341-348. 
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