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Somatic Diversification of Immunoglobulin Genes in Galt

Award Number: R01AI050260
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/05/2001
PERIOD OF PERFORMANCE END DATE: 07/31/2017

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Somatic Diversification of Immunoglobulin Genes in Galt - DESCRIPTION (provided by applicant): The intestinal commensal microbiota is required for development of lymphoid tissues and mucosal immunity in vertebrates. However, little is known of the mechanism by which these processes occur. Previous work in rabbits has demonstrated that the intestinal commensal microbiota is required for expansion of B cells and somatic diversification of Ig genes during development of the preimmune antibody repertoire, both of which occur in gut-associated lymphoid tissues (GALT). These processes occur within a few days after birth in an antigen- and T cell-independent manner, and surprisingly, they require activation of complement. We hypothesize a model for GALT development in which B cells enter GALT from the bone marrow soon after birth and migrate to the follicle-associated epithelium (FAE) and interact with C'-coated bacteria from the lumen. These complexes are then delivered to FDCs which provide stimulatory signals for B cell activation and upregulation of AID expression; within a few weeks after birth, essentially all Ig genes are somatically diversified, thereby providing the rabbits with a diverse antibody repertoire. The goal of this grant is to test this model of GALT development. In Aim 1 we will use soluble chemokine receptors to inhibit chemokine-driven migration and determine how the migration of B cells is altered; in Aim 2, we will use sterile GALT explants and TLR and NLR agonists and antagonists to determine the contribution of TLR and NLR ligands and IgM-binding bacterial superantigen-like molecules to B cell proliferation and Ig gene diversification; we will also use sterile explants of GALT as well as an in vitro FDC:B cell culture system to determine how complement activation contributes to GALT development. In Aim 3, we will search in gnotobiotic CD4-/- mice for GALT-like B cells that proliferate in an antigen and T-cell independent manner and undergo somatic diversification of the Ig genes. These experiments are important because they will begin to determine the mechanism by which commensal bacteria and complement contribute to development of mucosal lymphoid tissues and ultimately to human health and disease such as allergy and inflammatory bowel disease.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = -$27,950 )
2018	2015	LOYOLA UNIVERSITY OF CHICAGO	2160 S FIRST AVE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	13	11/13/2017	NON-COMPETING CONTINUATION	-$27,950
														Subtotal = -$27,950

Issue Date FY: 2015 ( Subtotal = $377,500 )
2015	2015	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	13	7/21/2015	NON-COMPETING CONTINUATION	$438,779
2015	2015	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	001	13	8/12/2015	NON-COMPETING CONTINUATION	-$61,279
														Subtotal = $377,500

Issue Date FY: 2014 ( Subtotal = $436,514 )
2014	2014	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	001	12	8/11/2014	SUPPLEMENT FOR EXPANSION	$59,014
2014	2014	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	12	7/17/2014	NON-COMPETING CONTINUATION	$377,500
														Subtotal = $436,514

Issue Date FY: 2013 ( Subtotal = $354,850 )
2013	2013	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	11	7/18/2013	NON-COMPETING CONTINUATION	$354,850
														Subtotal = $354,850

Issue Date FY: 2012 ( Subtotal = $377,500 )
2012	2012	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	10	7/25/2012	COMPETING CONTINUATION	$377,500
														Subtotal = $377,500

Issue Date FY: 2011 ( Subtotal = $313,204 )
2011	2011	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	9	9/1/2011	SUPPLEMENT FOR EXPANSION	$313,204
														Subtotal = $313,204

Issue Date FY: 2010 ( Subtotal = $360,555 )
2010	2010	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	9	5/20/2010	NON-COMPETING CONTINUATION	$360,555
														Subtotal = $360,555

Issue Date FY: 2009 ( Subtotal = $464,881 )
2009	2009	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	001	8	9/2/2009	NON-COMPETING CONTINUATION	$100,685
2009	2009	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	8	6/26/2009	NON-COMPETING CONTINUATION	$364,196
														Subtotal = $464,881

Issue Date FY: 2008 ( Subtotal = $364,196 )
2008	2008	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	7	5/9/2008	NON-COMPETING CONTINUATION	$364,196
														Subtotal = $364,196

Issue Date FY: 2007 ( Subtotal = $371,250 )
2007	2007	LOYOLA UNIVERSITY OF CHICAGO MEDICAL CENTER	6525 NORTH SHERIDAN STREET	CHICAGO	IL	60626	COOK	USA	Allergy and Infectious Diseases Research	000	6	6/18/2007	COMPETING CONTINUATION	$371,250
														Subtotal = $371,250

Issue Date FY: 2005 ( Subtotal = $333,000 )
2005	2005	LOYOLA UNIVERSITY MEDICAL CENTER							Allergy and Infectious Diseases Research	000	5	5/19/2005	NON-COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2004 ( Subtotal = $333,000 )
2004	2004	LOYOLA UNIVERSITY MEDICAL CENTER							Allergy and Infectious Diseases Research	000	4	5/12/2004	NON-COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2003 ( Subtotal = $333,000 )
2003	2003	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	3		NON-COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2002 ( Subtotal = $333,000 )
2002	2002	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	2	5/16/2002	NON-COMPETING CONTINUATION	$333,000
														Subtotal = $333,000

Issue Date FY: 2001 ( Subtotal = $299,700 )
2001	2001	LOYOLA UNIVERSITY MEDICAL CENTER	2160 SOUTH FIRST AVENUE	MAYWOOD	IL	60153	COOK	USA	Allergy and Infectious Diseases Research	000	1	8/2/2001	NEW	$299,700
														Subtotal = $299,700

Grand Total All Awards = $5,024,200

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Somatic Diversification of Immunoglobulin Genes in Galt

Award Number: R01AI050260

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/05/2001

PERIOD OF PERFORMANCE END DATE: 07/31/2017

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