NDLI: Modeling the clinical phenotype of BTK inhibition in the mature murine immune system.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Du, Sarah Schnute, Mark E. Rankin, Andrew L. Nickerson-Nutter, Cheryl L. Edmonds, Jason Messing, Dean Von Schack, David Ruzek, Melanie Cook, Tim A. Douhan, John Rodriguez, Varenka Seth, Nilufer Keegan, Sean Dunussi-Joannopoulos, Kyri Benson, Micah J. Benoit, Stephen
Description	Author Affiliation: Benson MJ ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Rodriguez V ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); von Schack D ( Biotherapeutics Clinical Research and Development, Pfizer Inc., Cambridge, MA 02140); Keegan S ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Cook TA ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Edmonds J ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Benoit S ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Seth N ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Du S ( Biotherapeutics Clinical Research and Development, Pfizer Inc., Cambridge, MA 02140); Messing D ( Biotherapeutics Pharmacokinetics, Dynamics, and Metabolism, Pfizer Inc., Cambridge, MA 02140); Nickerson-Nutter CL ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Dunussi-Joannopoulos K ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Rankin AL ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Ruzek M ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140); Schnute ME ( Biotherapeutics Medicinal Chemistry, Pfizer Inc., Cambridge, MA 02140.); Douhan J ( Biotherapeutics Immunoscience, Pfizer Inc., Cambridge, MA 02140)
Abstract	Inhibitors of Bruton's tyrosine kinase (BTK) possess much promise for the treatment of oncologic and autoimmune indications. However, our current knowledge of the role of BTK in immune competence has been gathered in the context of genetic inactivation of btk in both mice and man. Using the novel BTK inhibitor PF-303, we model the clinical phenotype of BTK inhibition by systematically examining the impact of PF-303 on the mature immune system in mice. We implicate BTK in tonic BCR signaling, demonstrate dependence of the T3 B cell subset and IgM surface expression on BTK activity, and find that B1 cells survive and function independently of BTK. Although BTK inhibition does not impact humoral memory survival, Ag-driven clonal expansion of memory B cells and Ab-secreting cell generation are inhibited. These data define the role of BTK in the mature immune system and mechanistically predict the clinical phenotype of chronic BTK inhibition.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	1
Volume Number	193
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2014-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	B-lymphocyte Subsets Immunology Immunity, Humoral Physiology Immunologic Memory Models, Immunological Protein-tyrosine Kinases Animals Cell Survival Drug Effects Genetics Immunoglobulin M Mice Mice, Inbred Cba Mice, Knockout Protein Kinase Inhibitors Pharmacology Antagonists & Inhibitors Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in