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Research Focus
My laboratory has a longstanding interest in antibodies to DNA.
- Anti-DNA antibodies occur in sera of patients with autoimmune disease
(lupus), and play a role in development of the disease. Our research
asks what the antibodies recognize in DNA and how the antibodies are
produced. Views of anti-DNA antibodies
- We have studied antibodies specific for a variety of helical forms
of DNA (eg B-DNA and Z-DNA), RNA and DNA-RNA hybrids, single-stranded
polynucleotides, and synthetic oligonucleotides to identify the nucleic
acid structures that can be recognized by antibodies. We have studied
antibodies induced by deliberate immunization as well as autoantibodies
associated with disease.

- We are especially interested in whether special sets of genes or gene
modifications are used to make the autoantibodies.
- We have tested whether different immunoglobulin gene repertoires are
expressed in infants, adults and elderly people, and whether autoantibody
formation is related to these repertoires.
- By cloning the genes used for anti-DNA antibodies into plasmids, we
use bacteria to produce the antigen-binding domain of the antibodies.
We then introduce mutations or exchange segments of different antibodies
to learn what parts are important for DNA binding.

- We are testing the idea that binding of self-antigens (autoreactivity)
plays a positive as well as negative role in selecting a primary repertoire
of antibody-forming B cells (R. S. Schwartz and B.. Stollar, Immunology
Today 15:27-32, 1994). We are studying B cell development in mice with
a ‘knock-in” transgene for a physiologically selected ssDNA-binding
antibody H domain.
- We use antibodies to measure unusual forms of DNA or other nucleic
acids and to study their changes in structure. In recent years we have
focused on left-handed Z-DNA. Antibodies have helped to reveal Z-DNA
structure in nature and to identify the conditions under which the usual
right-handed B-DNA can be converted to Z-DNA.
Recent Publications
Journal Articles
- Souza, Tatyana A; Stollar, B. David; Sullivan, John L; Luzuriaga,
Katherine; Thorley-Lawson, David A. (2005). “Peripheral B cells
latently infected with Epstein-Barr virus display molecular hallmarks
of classical antigen-selected memory B cells.” Proceedings of
the National Academy of Science 102(50): 18093-18098
- J.Li, E. D. Geissal, W. Li, and B. D. Stollar, (2005) Repertoire diversification
in mice with an IgH-locus-targeted transgene for the rearranged VH domain
of a physiologically selected anti-ssDNA antibody. Mol Immunol. 42:1475-84.
- S.Ghosh, A. C. Steere, B. D. Stollar, and B. T. Huber (2005) In situ
diversification of the antibody repertoire in chronic Lyme arthritis
synovium. J Immunol. 174:2860-9.
- M. Tam, S. E. Montgomery, M.Kekis, B. D. Stollar, G. B. Price, and
C. E. Pearson, (2003) Slipped (CTG).(CAG) repeats of the myotonic dystrophy
locus: surface probing with anti-DNA antibodies. J. Mol. Biol. 332:
585-600.
- E. Breitbart, X. Wang, L. S. Leka, G. E. Dallal, S. N. Meydani and
B. D. Stollar. (2002) Altered memory B cell homeostasis in human aging.
J. Gerontol. (Biol. Sci.). 57A:B304-B311.
- Stollar, B. D. (2002). Proteolytic Antibodies against Factor VIII
in Hemophilia A. N Engl J Med 346, 702-703.
- O'Connor, K. C., Nguyen, K., and Stollar, B. D. (2001). Recognition
of DNA by VH and Fv domains of an IgG anti-poly(dC) antibody with a
singly mutated VH domain. J Mol Recognit 14, 18-28.
- Li, J., Fernandez, L., O'Connor, K. C., Imanishi-Kari, T., and Stollar,
B. D. (2001). The rearranged V(H) domain of a physiologically selected
anti-single- stranded DNA antibody as a precursor for formation of IgM
and IgG antibodies to diverse antigens. J Immunol 167, 3746-3755.
- O'Connor, K. C., Ghatak, S., and Stollar, B. D. (2000). Use of hydrophobic
interaction chromatography to separate recombinant antibody fragments
from associated bacterial chaperone protein GroEL. Anal Biochem 278,
239-241.
- Breitbart, E., and Stollar, B. D. (2000). Aging and the human immune
system. Isr Med Assoc J 2, 703-707.
- Wang, X., and Stollar, B. D. (2000). Human immunoglobulin variable
region gene analysis by single cell RT-PCR. J Immunol Methods 244, 217-225.
- Wang, X., and Stollar, B. D. (1999). Immunoglobulin VH gene expression
in human aging. Clin Immunol 93, 132-142.
- Chen, Y., and Stollar, B. D. (1999). DNA binding by the VH domain
of anti-Z-DNA antibody and its modulation by association of the VL domain.
J Immunol 162, 4663-4670.
- Jang, Y. J., Sanford, D., Chung, H. Y., Baek, S. Y., and Stollar,
B. D. (1998). The structural basis for DNA binding by an anti-DNA autoantibody.
Mol Immunol 35, 1207-1217.
- Lecerf, J. M., Chen, Y., Richalet-Secordel, P., Wang, X., and Stollar,
B. D. (1998). Autoreactivity of human VH domains from cDNA libraries:
analysis with a bacterial expression system. J Immunol 161, 1274-1283.
- Stollar, B. D., Lecerf, J. M., and Hirabayashi, Y. (1997). The role
of autoreactivity in B cell selection. Ann N Y Acad Sci 815, 30-39.
Figure 1 and 2.
- Bacolla, A., Gellibolian, R., Shimizu, M., Amirhaeri, S., Kang, S.,
Ohshima, K., Larson, J. E., Harvey, S. C., Stollar, B. D., and Wells,
R. D. (1997). Flexible DNA: genetically unstable CTG.CAG and CGG.CCG
from human hereditary neuromuscular disease genes. J Biol Chem 272,
16783-16792.
- Stollar, B. D. (1997). Bacterial expression of anti-DNA antibody domains.
Methods 11, 12-19.
- Jang, Y. J., Lecerf, J. M., and Stollar, B. D. (1996). Heavy chain
dominance in the binding of DNA by a lupus mouse monoclonal autoantibody.
Mol Immunol 33, 197-210.
- Kubota, T., Watanabe, N., Kanai, Y., and Stollar, B. D. (1996). Enhancement
of oxidative cleavage of DNA by the binding sites of two anti-double-stranded
DNA antibodies. J Biol Chem 271, 6555-6561.
- Kalsi, J. K., Martin, A. C., Hirabayashi, Y., Ehrenstein, M., Longhurst,
C. M., Ravirajan, C., Zvelebil, M., Stollar, B. D., Thornton, J. M.,
and Isenberg, D. A. (1996). Functional and modelling studies of the
binding of human monoclonal anti-DNA antibodies to DNA. Mol Immunol
33, 471-483.
- Roben, P., Barbas, S. M., Sandoval, L., Lecerf, J. M., Stollar, B.
D., Solomon, A., and Silverman, G. J. (1996). Repertoire cloning of
lupus anti-DNA autoantibodies. J Clin Invest 98, 2827-2837.
- Polymenis, M., and Stollar, B. D. (1995). Domain interactions and
antigen binding of recombinant anti-Z-DNA antibody variable domains.
The role of heavy and light chains measured by surface plasmon resonance.
J Immunol 154, 2198-2208.
- Hirabayashi, Y., Lecerf, J. M., Dong, Z., and Stollar, B. D. (1995).
Kinetic analysis of the interactions of recombinant human VpreB and
Ig V domains. J Immunol 155, 1218-1228. Model of
B cell development
Reviews and Chapters
- 1. Y. J. Jang and B. D. Stollar, Anti-DNA antibodies: aspects of structure
and pathogenicity, Cellular and Molecular Life Sciences, 60: 309-320,
2003.
- E. Breitbart and B.D. Stollar, Aging and the human immune system,
Israel Medical Association Journal, 2:703-707, 2000.
- B.D. Stollar, J-M Lecerf and Y. Hirabayashi. The role of autoreactivity
in B cell selection. Annals of the New York Academy of Sciences, 815:30-39,
1997.
- B.D. Stollar, The expressed heavy chain V gene repertoire of circulating
B cells in normal adults. Annals of the New York Academy of Sciences
764:265-274, 1995.
- R. S. Schwartz and B.. Stollar, Heavy chain directed B cell maturation:
continuous clonal selection beginning at the pre-B cell stage. Immunology
Today 15:27-32, 1994.
- B.D. Stollar, Molecular analysis of anti-DNA antibodies, FASEB J.
8:337-342, 1994.
- B.D. Stollar, Immunochemical analyses of nucleic acids. Prog. Nucleic
Acids Res. Mol. Biol. 42:39-77, 1992.
Lab Group
Biochemistry Graduate Student
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