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Complement system and humoral immunity

Award Number: R01AI039246
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: 08/15/2011
PERIOD OF PERFORMANCE END DATE: 07/31/2015

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Complement system and humoral immunity - DESCRIPTION (provided by applicant): How antigens (and pathogens) enter the B cell follicles of secondary lymphoid tissues and are acquired by B cells has been a long-standing enigma. However, recent papers have identified at least two major pathways in which lymph-borne antigens enter the B cell area and are either acquired by cognate B cells or retained on follicular dendritic cells (FDC). Importantly, the nature of the antigen is a major factor. While small soluble antigens enter via a network of conduits formed by fibroblast reticular cells, larger protein immune complexes and particulate antigens are bound by subcapsular sinus macrophages and shuttled to the underlying B cells where they are captured by cognate B or bound by naive B cells via CD21 receptor. How the antigen is transferred to the FDC remains unclear. Most recently, we reported a third pathway in which lymph-borne influenza (UV-inactivated) was rapidly opsonized via mannan binding lectin and bound by macrophages lining both the subcapsular sinus and the medullary regions. Notably, macrophages are not required for humoral immunity in this pathway. Instead, dendritic cells residing in the medullary region of the LN capture virus via SIGN-R1 and appear to directly transport the viral particles to the B cell area. Whether the virus is handed off directly to FDC or to other intermediates in the follicles is not known. The overall goal of this proposal is to clarify how B cell antigen is delivered and off-loaded onto the FDC surface. Two aims are proposed. (1) Test the hypothesis that B cells transfer antigen to FDC in a 3-step process. (2) Test the hypothesis that LN resident mDC capture antigens via SIGN-R1 and traffick to FDC. )


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: 2014 ( Subtotal = $477,449 )
2014	2014	CHILDREN'S HOSPITAL CORPORATION	300 LONGWOOD AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	19	7/17/2014	NON-COMPETING CONTINUATION	$477,449
														Subtotal = $477,449

Issue Date FY: 2013 ( Subtotal = $429,035 )
2013	2013	CHILDREN'S HOSPITAL CORPORATION	300 LONGWOOD AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	18	7/26/2013	NON-COMPETING CONTINUATION	$448,802
2013	2012	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	16	12/12/2012	NON-COMPETING CONTINUATION	-$344,999
2013	2012	CHILDREN'S HOSPITAL CORPORATION	300 LONGWOOD AVENUE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	17	12/12/2012	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$325,232
														Subtotal = $429,035

Issue Date FY: 2012 ( Subtotal = $517,500 )
2012	2012	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	16	6/28/2012	NON-COMPETING CONTINUATION	$517,500
														Subtotal = $517,500

Issue Date FY: 2011 ( Subtotal = $517,500 )
2011	2011	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	15	8/15/2011	COMPETING CONTINUATION	$525,000
2011	2011	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	15	8/16/2011	COMPETING CONTINUATION	-$7,500
														Subtotal = $517,500

Issue Date FY: 2010 ( Subtotal = $495,090 )
2010	2010	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	14	2/18/2010	NON-COMPETING CONTINUATION	$495,090
														Subtotal = $495,090

Issue Date FY: 2009 ( Subtotal = $500,090 )
2009	2009	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	13	2/23/2009	NON-COMPETING CONTINUATION	$450,080
2009	2009	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	13	6/29/2009	NON-COMPETING CONTINUATION	$50,010
														Subtotal = $500,090

Issue Date FY: 2008 ( Subtotal = $451,033 )
2008	2008	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	12	3/4/2008	NON-COMPETING CONTINUATION	$451,033
														Subtotal = $451,033

Issue Date FY: 2007 ( Subtotal = $459,769 )
2007	2007	CBR INSTITUTE FOR BIOMEDICAL RESEARCH INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	11	3/7/2007	NON-COMPETING CONTINUATION	$459,769
														Subtotal = $459,769

Issue Date FY: 2006 ( Subtotal = $473,500 )
2006	2006	CBR INSTITUTE FOR BIOMEDICAL RESEARCH INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	10	3/9/2006	COMPETING CONTINUATION	$473,500
														Subtotal = $473,500

Issue Date FY: 2004 ( Subtotal = $375,892 )
2004	2004	CENTER FOR BLOOD RESEARCH, INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	9	5/6/2004	NON-COMPETING CONTINUATION	$375,892
														Subtotal = $375,892

Issue Date FY: 2003 ( Subtotal = $375,988 )
2003	2003	CENTER FOR BLOOD RESEARCH, INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	8		NON-COMPETING CONTINUATION	$375,988
														Subtotal = $375,988

Issue Date FY: 2002 ( Subtotal = $338,241 )
2002	2002	CENTER FOR BLOOD RESEARCH, INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	7	7/16/2002	NON-COMPETING CONTINUATION	$338,241
														Subtotal = $338,241

Issue Date FY: 2001 ( Subtotal = $338,553 )
2001	2001	CENTER FOR BLOOD RESEARCH, INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	6	9/17/2001	COMPETING CONTINUATION	$338,553
														Subtotal = $338,553

Issue Date FY: 2000 ( Subtotal = $354,879 )
2000	2000	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	7/25/2000	NON-COMPETING CONTINUATION	$354,879
														Subtotal = $354,879

Issue Date FY: 1999 ( Subtotal = $339,103 )
1999	1999	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	6/30/1999	NON-COMPETING CONTINUATION	$339,103
														Subtotal = $339,103

Issue Date FY: 1998 ( Subtotal = $327,026 )
1998	1998	IMMUNE DISEASE INSTITUTE INC	800 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	9/7/1998	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$327,026
														Subtotal = $327,026

Grand Total All Awards = $6,770,648

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Complement system and humoral immunity

Award Number: R01AI039246

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: 08/15/2011

PERIOD OF PERFORMANCE END DATE: 07/31/2015

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