Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination

Publication Date:
2018-04-13
Publisher:
American Association for the Advancement of Science (AAAS)
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
Chemistry and Pharmacology
Geosciences
Computer Science
Medicine
Natural Sciences in General
Physics
Keywords:
Cell Biology, Immunology
Published by:
http://www.aaas.org/
_version_ 1836398891274076160
autor Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
beschreibung Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.
citation_standardnr 6233640
datenlieferant ipn_articles
feed_id 25
feed_publisher American Association for the Advancement of Science (AAAS)
feed_publisher_url http://www.aaas.org/
insertion_date 2018-04-13
journaleissn 1095-9203
journalissn 0036-8075
publikationsjahr_anzeige 2018
publikationsjahr_facette 2018
publikationsjahr_intervall 7984:2015-2019
publikationsjahr_sort 2018
publisher American Association for the Advancement of Science (AAAS)
quelle Science
relation http://science.sciencemag.org/cgi/content/short/360/6385/223?rss=1
schlagwort Cell Biology, Immunology
search_space articles
shingle_author_1 Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
shingle_author_2 Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
shingle_author_3 Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
shingle_author_4 Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
shingle_catch_all_1 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
Cell Biology, Immunology
Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.
Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_2 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
Cell Biology, Immunology
Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.
Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_3 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
Cell Biology, Immunology
Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.
Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_catch_all_4 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
Cell Biology, Immunology
Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.
Burnett, D. L., Langley, D. B., Schofield, P., Hermes, J. R., Chan, T. D., Jackson, J., Bourne, K., Reed, J. H., Patterson, K., Porebski, B. T., Brink, R., Christ, D., Goodnow, C. C.
American Association for the Advancement of Science (AAAS)
0036-8075
00368075
1095-9203
10959203
shingle_title_1 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
shingle_title_2 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
shingle_title_3 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
shingle_title_4 Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
timestamp 2025-06-30T23:34:17.262Z
titel Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
titel_suche Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination
topic W
V
TE-TZ
SQ-SU
WW-YZ
TA-TD
U
uid ipn_articles_6233640