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Di Niro R.,University of Pittsburgh | Di Niro R.,Yale University | Lee S.-J.,University of California at Davis | Vander Heiden J.A.,Yale University | And 11 more authors.
Immunity | Year: 2015

The B cell response to Salmonella typhimurium (STm) occurs massively at extrafollicular sites, without notable germinal centers (GCs). Little is known in terms of its specificity. To expand the knowledge ofantigen targets, we screened plasmablast (PB)-derived monoclonal antibodies (mAbs) for Salmonella specificity, using ELISA, flow cytometry, and antigen microarray. Only a small fraction (0.5%-2%) of the response appeared to be Salmonella-specific. Yet, infection of mice with limited B cell receptor (BCR) repertoires impaired the response, suggesting that BCR specificity was important. We showed, using laser microdissection, that somatic hypermutation (SHM) occurred efficiently at extrafollicular sites leading to affinity maturation that in turn led to detectable STm Ag-binding. These results suggest a revised vision of how clonal selection and affinity maturation operate in response to Salmonella. Clonal selection initially is promiscuous, activating cells with virtually undetectable affinity, yet SHM and selection occur during the extrafollicular response yielding higher affinity, detectable antibodies. © 2015 Elsevier Inc.


Stern J.N.H.,Yale University | Stern J.N.H.,Hofstra University | Yaari G.,Yale University | Yaari G.,Bar - Ilan University | And 16 more authors.
Science Translational Medicine | Year: 2014

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) characterized by autoimmunemediated demyelination and neurodegeneration. The CNS of patients withMSharbors expanded clones of antigen-experienced B cells that reside in distinct compartments including the meninges, cerebrospinal fluid (CSF), and parenchyma. It is not understood whether this immune infiltrate initiates its development in the CNS or in peripheral tissues. B cells in the CSF can exchange with those in peripheral blood, implying that CNS B cells may have access to lymphoid tissue that may be the specific compartment(s) in which CNS-resident B cells encounter antigen and experience affinitymaturation. Paired tissues were used to determine whether the B cells that populate the CNS mature in the draining cervical lymph nodes (CLNs). High-throughput sequencing of the antibody repertoire demonstrated that clonally expanded B cells were present in both compartments. Founding members of clones were more often found in the draining CLNs. More mature clonal members derived from these founders were observed in the draining CLNs and also in the CNS, including lesions. These data provide new evidence that B cells traffic freely across the tissue barrier, with the majority of B cell maturation occurring outside of the CNS in the secondary lymphoid tissue. Our study may aid in further defining the mechanisms of immunomodulatory therapies that either deplete circulating B cells or affect the intrathecal B cell compartment by inhibiting lymphocyte transmigration into the CNS.


Patent
Abvitro Inc. | Date: 2014-03-14

Provided herein are methods and composition for immune repertoire sequencing and single cell barcoding. The methods and compositions can be used to heavy and light chain antibody sequences originating from a single cell, antibody discovery, disease and immune diagnostics, and low error sequencing.


Patent
AbVitro Inc. | Date: 2014-03-14

Provided herein are methods and composition for immune repertoire sequencing and single cell barcoding for heavy and IgL pairing if antibodies.


Patent
AbVitro Inc. | Date: 2015-09-15

Provided herein are methods and composition for immune repertoire sequencing and single cell barcoding. The methods and compositions can be used to pair any two sequences originating from a single cell, such as heavy and light chain antibody sequences, alpha and beta chain T-cell receptor sequences, or gamma and delta chain T-cell receptor sequences, for antibody and T-cell receptor discovery, disease and immune diagnostics, and low error sequencing.


Trademark
AbVitro Inc. | Date: 2014-10-09

diagnostic reagents, and immunological substrates and antigens for use in immunological testing and detection of antibodies for medical laboratory or clinical purposes; assays for research, scientific and clinical laboratory use; chemical, biochemical, biological, and biotechnological preparations, namely, antibodies for use in the development or manufacture of immunological reagents and assays for industrial and scientific use; biological preparations, namely, antibodies for laboratories, diagnostics and analytics for scientific or research use. medical assays for testing body fluids for the detection of antibodies; medical diagnostic immunoassays for antibody screening and detection; diagnostic pharmaceutical preparations, namely, antibodies and fragments of antibodies for laboratories, diagnostics, and analytics for human and veterinary medical diagnostic use for use in disease testing; pharmaceutical and veterinary preparations and substances, namely, antibodies and fragments of antibodies for use in disease testing. biochemical research and development.


Trademark
AbVitro Inc. | Date: 2014-10-09

diagnostic reagents, and immunological substrates and antigens for use in immunological testing and detection of antibodies for medical laboratory or clinical purposes; assays for research, scientific and clinical laboratory use; chemical, biochemical, biological, and biotechnological preparations, namely, antibodies for use in the development or manufacture of immunological reagents and assays for industrial and scientific use; biological preparations, namely, antibodies for laboratories, diagnostics and analytics for scientific or research use. medical assays for testing body fluids for the detection of antibodies; medical diagnostic immunoassays for antibody screening and detection; diagnostic pharmaceutical preparations, namely, antibodies and fragments of antibodies for laboratories, diagnostics, and analytics for human and veterinary medical diagnostic use for use in disease testing; pharmaceutical and veterinary preparations and substances, namely, antibodies and fragments of antibodies for use in disease testing. biochemical research and development.


Trademark
AbVitro Inc. | Date: 2014-10-09

diagnostic reagents, and immunological substrates and antigens for use in immunological testing and detection of antibodies for medical laboratory or clinical purposes; assays for research, scientific and clinical laboratory use; chemical, biochemical, biological, and biotechnological preparations, namely, antibodies for use in the development or manufacture of immunological reagents and assays for industrial and scientific use; biological preparations, namely, antibodies for laboratories, diagnostics and analytics for scientific or research use. medical assays for testing body fluids for the detection of antibodies; medical diagnostic immunoassays for antibody screening and detection; diagnostic pharmaceutical preparations, namely, antibodies and fragments of antibodies for laboratories, diagnostics, and analytics for human and veterinary medical diagnostic use for use in disease testing; pharmaceutical and veterinary preparations and substances, namely, antibodies and fragments of antibodies for use in disease testing. biochemical research and development.


Trademark
AbVitro Inc. | Date: 2014-10-09

diagnostic reagents, and immunological substrates and antigens for use in immunological testing and detection of antibodies for medical laboratory or clinical purposes; assays for research, scientific and clinical laboratory use; chemical, biochemical, biological, and biotechnological preparations, namely, antibodies for use in the development or manufacture of immunological reagents and assays for industrial and scientific use; biological preparations, namely, antibodies for laboratories, diagnostics and analytics for scientific or research use. medical assays for testing body fluids for the detection of antibodies; medical diagnostic immunoassays for antibody screening and detection; diagnostic pharmaceutical preparations, namely, antibodies and fragments of antibodies for laboratories, diagnostics, and analytics for human and veterinary medical diagnostic use for use in disease testing; pharmaceutical and veterinary preparations and substances, namely, antibodies and fragments of antibodies for use in disease testing. biochemical research and development.


Trademark
AbVitro Inc. | Date: 2015-10-07

diagnostic reagents, and immunological substrates and antigens for use in immunological testing and detection of antibodies or antigens for medical laboratory or clinical purposes; assays for research, scientific and clinical laboratory use; chemical, biochemical, biological, and biotechnological preparations, namely, antibodies or antigens for use in the development or manufacture of immunological reagents and assays for industrial and scientific use; biological preparations, namely, antibodies or antigens for laboratories, diagnostics and analytics for scientific or research use. medical assays for testing body fluids for the detection of antibodies or antigens; medical diagnostic immunoassays for antibody or antigen screening and detection; diagnostic pharmaceutical preparations, namely, antibodies, fragments of antibodies, antigens, and fragments of antigens for laboratories, diagnostics, and analytics for human and veterinary medical diagnostic use for use in disease testing; pharmaceutical and veterinary preparations and substances, namely, antibodies, fragments of antibodies, antigens, and fragments of antigens for use in disease testing. biochemical research and development.

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