mors at high frequency in double-transgenic 
mice. Oncogene 6:1941-1948. 
Morrow, M.A., Lee, G., Gillis, S., Yancopoulos, 
G.D., and Alt, F.W. 1992. Interleukin-7 induces 
N-myc and c-myc expression in normal precursor 
B lymphocytes. Genes Dev 6:61-70. 
Oltz, E.M., Yancopoulos, G.D., Morrow, M.A., Ro- 
link. A., Lee, G., Wong, F., Kaplan, K., Gillis, S., 
Melchers, F., and Alt, F.W. 1992. A novel regula- 
tory myosin light chain gene distinguishes pre-B 
cell subsets and is IL-7 inducible. EMBO J 
11:2759-2767. 
Rothman, P., Li, S.C., Gorham, B., Glimcher, L., 
Alt, P., and Boothby, M. 1991 . Identification of a 
conserved lipopolysaccharide-plus-interleukin-4- 
responsive element located at the promoter of 
germ line e transcripts. Mol Cell Biol 11:5551- 
5561. 
Schultz, C.L., Rothman, P., Kuhn, R., Kehry, M., 
Miiller, W., Rajewsky, K., Alt, F., and Coffman, 
R.L. 1992. T helper cell membranes promote 
Il-4-independent expression of germ-line C7I 
transcripts in B cells. J Immunol 149:60-64. 
Shinkai, Y., Rathbun, G., Lam, K. P., Oltz, E.M., 
Stewart, V., Mendelsohn, M., Charron, J., 
Datta, M., Young, F., Stall, A.M., and Alt, F.W. 
1992. RAG- 2 -deficient mice lack mature lympho- 
cytes owing to inability to initiate V(D)J rear- 
rangement. Cf?// 68:855-867. 
Smith, R.K., Zimmerman, K., Yancopoulos, G.D., 
Ma, A., and Alt, F.W. 1992. Transcriptional 
down-regulation of N-myc expression during 
B-cell development. Mol Cell Biol 12:1578- 
1584. 
Timmers, E., de Weers, M., Alt, F.W., Hendriks, 
R.W., and Schuurman, R.K.B. 1991. X-linked 
agammaglobulinemia. Clin Immunol Immuno- 
pathol 6l:S85-S95. 
Timmers, E., Kenter, M., Thompson, A., Kraakman, 
M.E.M., Berman, J.E., Alt, F.W., and Schuurman, 
R.K.B. 1991. Diversity of immunoglobulin heavy 
chain gene segment rearrangement in B lympho- 
blastoid cell lines from X-linked agammaglobu- 
linemia patients. EurJImmunol2l:2555-2565. 
Wang, Y., Sugiyama, H., Axelson, H., Panda, C.K., 
Babonits, M., Ma, A., Steinberg, J.M., Alt, F.W., 
Klein, G., andWiener, F. 1992. Functional homol- 
ogy between N-myc and c-myc in murine plasma- 
cytomagenesis: plasmacytoma development in N- 
mjc transgenic mice. Oncogene 1 -.1241-1241 . 
COMPLEMENT SYSTEM 
John P. Atkinson, M.D., Investigator 
The complement (C) system helps the host pre- 
vent infections. It is part of an innate immune sys- 
tem with the capacity to recognize nonself (the al- 
ternative pathway) and promote the inflammatory 
response. It is also a potent effector pathway for an- 
tibody (the classical pathway). 
When the C system is activated by the binding of 
antibody to antigen, or by other means, C proteins, 
particularly an activated fragment of C3, bind cova- 
lently to antigens as part of the normal immune re- 
sponse. Such binding also occurs to self tissue in 
disease states, as part of a pathologic (autoimmune) 
response. Deposited C3 fragments serve as ligands 
for C receptors that facilitate the elimination of ma- 
terials to which C3 is bound. 
Regulatory proteins in plasma and on autologous 
tissue prevent the inappropriate activation and am- 
plification of the C system by controlling this criti- 
cal step of C3 deposition. As a result, these regula- 
tors inhibit C activation in plasma or on self tissue 
and allow C to amplify only on a foreign target. 
Regulators of Complement Activation (RCA) 
The RCA is a multigene family of C receptor and 
regulatory proteins. The members of this family are 
related functionally (the proteins bind to C compo- 
nents attached to targets) , genetically (the genes are 
located in a tight cluster on the long arm of chromo- 
some 1), and structurally (each protein is largely 
composed of a tandem array of 60-amino acid, cys- 
teine-rich, repeating modules). Analyses of these 
proteins have provided insights into the mecha- 
nisms whereby C recognizes and destroys microbes 
while at the same time protecting self tissue. Manip- 
ulation of the C regulatory proteins has important 
implications for tumor, transplantation, and repro- 
ductive immunology, as well as autoimmunity. 
The human RCA gene cluster has been character- 
ized with yeast artificial chromosomes (YACs). 
Members of this family include decay-accelerating 
factor (DAF), complement receptors 1 and 2 (CRl 
and CR2), membrane cofactor protein (MCP), 
C4-binding protein (C4bp), and factor H. Although 
IMMUNOLOGY 305 
