the IL-1 convertase were supported by funds from 
the Monsanto Company.) 
Dr. Chaplin is also Associate Professor of Medi- 
cine, Genetics, and Molecular Microbiology at 
Washington University School of Medicine and 
Assistant Physician at Barnes Hospital, St. Louis. 
Books and Chapters of Books 
Bora, N.S., Chaplin, D.D., and Atkinson, J.P. 
1992. Restriction fragment length polymor- 
phisms of proteins of the complement system. In 
Manual of Clinical Laboratory Lmmunology 
(Rose, N.E., de Macario, E.C., Fahey, J.L., Fried- 
man, H., and Penn, G.M., Eds.). Washington, DC: 
American Society for Microbiology, pp 153-155. 
Chaplin, D.D., and Hogquist, K.A. 1992. Interac- 
tions between TNF and interleukin-1 . In Tumor 
Necrosis Factors: The Molecules and Their 
Emerging Role in Medicine (Beutler, B., Ed.). 
New York: Raven, pp 197-220. 
Articles 
Domalik, L.J., Chaplin, D.D., Kirkman, M.S., Wu, 
R.C., Liu, W.W., Howard, T.A., Seldin, M.F., and 
Parker, K.L. 1991. Different isozymes of mouse 
1 1 /3-hydroxylase produce mineralocorticoids and 
glucocorticoids. Mol Endocrinol 5:1853-1861. 
Geraghty, D.E., Pei, J., Lipsky, B., Hansen, J.A., 
Taillon-Miller, P., Bronson, S.K., and Chaplin, 
D.D. 1992. Cloning and physical mapping of the 
HLA class I region spanning the LLLA E-to HLA-F 
interval by using yeast artificial chromosomes. 
Proc Natl Acad Sci USA 89:2669-2673- 
Hogquist, K.A., Nett, M.A., Unanue, E.R., and 
Chaplin, D.D. 1991. Interleukin 1 is processed 
and released during apoptosis. Proc Natl Acad Sci 
USA 88:8485-8489. 
Hogquist, K.A., Unanue, E.R., and Chaplin, D.D. 
1991. Release of IL-1 by mononuclear phago- 
cytes. //mmMwo/ 147:2181-2186. 
Howard, A.D., Kostura, M.J., Thornberry, N., Ding, 
G.J.F., Limjuco, G., Weidner, J., Salley, J.P., 
Hogquist, K.A., Chaplin, D.D., Mumford, 
R.A., Schmidt, J.A., and Tocci, M.J. 1991. IL-1- 
converting enzyme requires aspartic acid residues 
for processing of the IL-ljS precursor at two dis- 
tinct sites and does not cleave 31-kDa IL-la.//m- 
munol 147:2964-2969. 
Kozono, H., Bronson, S.K., Taillon-Miller, P., 
Moorti, M.K., Jamry, I., and Chaplin, D.D. 
1991 . Molecular linkage of the HLA-DR, HLA-DQ, 
and HLA-DO genes in yeast artificial chromo- 
somes. Genomics 11:577-586. 
Parimoo, S., Patanjali, S.R., Shukia, H., Chaplin, 
D.D., and Weissman, S.M. 1991. cDNA selection: 
efficient PGR approach for the selection of cDNAs 
encoded in large chromosomal DNA fragments. 
Proc Natl Acad Sci USA 88:9623-9627. 
DEVELOPMENT OF THE IMMUNE SYSTEM 
Max D. Cooper, M.D., Investigator 
Developmental biology of the immune system is 
the theme of Dr. Cooper's laboratory, in which lym- 
phoid differentiation of hematopoietic stem cells 
is explored. The goal is to define the abnormali- 
ties in T and B cell differentiation that occur in hu- 
man immunodeficiency diseases and lymphoid 
malignancies. 
B Cell Recognition as a Function 
of Differentiation 
Normally we produce ~ 10'° B cells each day in 
our bone marrow. This differentiation process al- 
lows the continual renewal of the B cell repertoire 
throughout life. The process begins when hemato- 
poietic stem cell progeny are triggered by contact 
with neighboring stromal cells and their soluble 
products to become lymphoid progenitors. Cells 
thus influenced to differentiate along this lymphoid 
pathway express the transmembrane CD 19 mole- 
cule, and their progression is marked by the rear- 
rangement and expression of immunoglobulin (Ig) 
heavy-chain (HC) and light-chain (LC) genes. 
VDJh gene rearrangements usually occur first to 
allow nHC expression, and VJl rearrangements then 
occur to allow LC expression. Progenitor B cells 
thus lack both HC and LC, while daughter precursor 
B cells produce /x chains that are largely retained in 
the endoplasmic reticulum by a protein called BiP. 
Following LC gene rearrangement and expression, 
pre-B cells are converted into B cells as their k or X 
LC genes displace BiP to allow cell surface expres- 
sion of IgM antigen receptors. 
The discovery of surrogate (xp) LC genes that do 
not require rearrangement to be expressed in pro-B 
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