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Volume 8, Issue 3 (Suppl) J Clin Cell Immunol, an open access journal
ISSN: 2155-9899
Page 34
Notes:
conferenceseries.com
June 29-July 01, 2017 Madrid, Spain
8th European
Immunology Conference
Euro Immunology 2017
June 29-July 01, 2017
Regulation of diversification and affinity maturation of antibodies
B-lymphocytes can modify their immunoglobulin (Ig) genes to generate antibodies with a new isotype and enhanced
affinity. Activation-induced cytidine deaminase (AID) is the key mutagenic enzyme that initiates these processes. How
somatic hypermutation (SH) and class switch recombination (CSR) are targeted and regulated is key to understanding how we
achieve good antibodies. The trans-acting factors mediating specific targeting of AID and thereby SH and CSR have remained
elusive. No direct coupling between a transcription factor and the specific targeting of AID has been demonstrated, and how
AID is recruited is still a big mystery. We show that mutant E2A with defect inhibition by the Ca2+-sensor protein calmodulin
results in reduced B cell receptor- (BCR-), IL4- plus CD40 ligand-stimulated CSR to IgE. AID is shown to be together with
the transcription factors E2A, PAX5 and IRF4 in a complex on key sequences of the Igh locus in activated mouse splenic B
cells. Calmodulin shows proximity with them after BCR stimulation. Direct protein-protein interactions are shown to enable
formation of the complex. BCR signaling reduces binding of the proteins to some of the target sites on the Igh locus, and
calmodulin resistance of E2A blocks this reduction. Thus, E2A, AID, PAX5 and IRF4 are components of a CSR and SH complex
that calmodulin binding redistributes on the Igh locus. We present also regulation of a “mutasome”, the protein complex that
enables repair at high error rate of the uracils made by AID on Ig genes but not on most other genes.
Biography
Thomas Grundström completed his doctorate at Umeå University in 1981 and his Medical degree in 1982. Dr. Grundström was post-doc 1982-1984 in the laboratory of
prof. Pierre Chambon, Strasbourg, France, where he characterised the first discovered enhancer of transcription. He is professor at the department of Molecular Biology
at Umeå University since 1994. Dr. Grundström discovered the first direct Ca2+/calmodulin inhibition of a transcription factor (Corneliusen et al., Nature, 1994) and has
characterized the Ca2+ regulation of many regulatory proteins with a focus on the immune system. Dr. Grundström is presently studying regulation of production of high
affinity antibodies.
Thomas Grundström
Umeå University, Sweden
Thomas Grundström, J Clin Cell Immunol 2017, 8:3(Suppl)
DOI: 10.4172/2155-9899-C1-035