The present invention contemplates that complement receptor 1 and 2 may play a role in the induction of regulatory B cells under inflammatory conditions that accompany immune-mediated diseases. For example, long noncoding RNA may regulation transcription of the complement receptor I gene, thereby resulting in an induction and/or suppression of regulatory B cells. Such long noncoding RNA in mature B cells may be specifically targeted to modify complement receptor 1 levels and induce or suppress the generation of antigen-specific regulatory B cells, thereby modifying the course of immune mediated diseases including, but not limited to, autoimmune disease, cancer, and infection.

This invention provides methods to evaluate therapeutic efficacy of therapeutic monoclonal antibodies.

Methods and devices are provided herein for identifying a cell population comprising an effector cell that exerts an extracellular effect. In one embodiment the method comprises retaining in a microreactor a cell population comprising one or more effector cells, wherein the contents of the microreactor further comprise a readout particle population comprising one or more readout particles, incubating the cell population and the readout particle population within the microreactor, assaying the cell population for the presence of the extracellular effect, wherein the readout particle population or subpopulation thereof provides a direct or indirect readout of the extracellular effect, and determining, based on the results of the assaying step, whether one or more effector cells within the cell population exerts the extracellular effect on the readout particle. If an extracellular effect is measured, the cell population is recovered for further analysis to determine the cell or cells responsible for the effect.

This invention concerns compositions and methods of treating or diagnosing inflammatory disorders and other disorders, as well as compositions and methods of treating HIV.

In one aspect, methods of generating human monoclonal antibodies that specifically binds to an allergen are provided. In some embodiments, the monoclonal antibodies are generated from sequences identified from isolated single B cells from a human subject who is allergic to the allergen.

A 3D microfluidic device for use as an in vitro lymph node is described. The microfluidic device has a body with a semi-circular inner wall and a first channel located adjacent along the semi-circular inner wall, the first channel corresponding to a subcapsular sinus region of a lymph node, a second channel located adjacent the first channel, the second channel corresponding to a reticular network, and a bottom cavity and top cavity, centrally located, corresponding to a paracortex and follicle of a lymph node, respectively. The various compartments of the device are separated by circumferentially and horizontally located rows of micro-pillars. A lab-on-a-chip device incorporating the microfluidic device is also described.

Prediction of a clinical response to a therapy of a subject with an autoimmune disease based on B cell immune repertoire may include determining a plurality of clone frequencies in a biological sample from the subject, wherein the clone frequencies include: IgM, IgD, IgG3, IgG4, IgA, IgM with first somatic hypermutation (SHM) level, IgG1 with second SHM level. A plurality of decision criteria may be applied to features including the plurality of clone frequencies. Each decision criterion applies at least one threshold to a feature, wherein the plurality of decision criteria provides a plurality of output values. The plurality of output values may be summed and a sigmoid transformation may be applied to the summed value to form a prediction value. The prediction value may be compared to a final threshold to identify the subject as a likely responder or non-responder to an autoimmune disease therapy.

This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods involve the steps of (a) culturing lymphocytes from the subject under suitable conditions; (b) measuring the amount of PKCε in the cultured lymphocytes; and (c) comparing the measurement of step (b) with a suitable control.

The present disclosure relates to a method for simultaneous detection of antigens and antigen specific antibodies. LIBRA-seq (Linking B Cell Receptor to Antigen specificity through sequencing) is developed to simultaneously recover both antigen specificity and paired heavy and light chain BCR sequence. LIBRA-seq is a next-generation sequencing-based readout for BCR-antigen binding interactions that utilizes oligonucleotides (oligos) conjugated to recombinant antigens.

The present invention relates to the field of producing, identifying, and selecting biological binding molecules, e.g. in particular antibodies or fragments thereof, which selectively bind to somatically hypermutated B-cell receptors or B-cell receptor complexes. The method is used in order to select a biological binding molecule which specifically binds to a B-cell receptor having hypermutated regions as the target receptor, but not to a B-cell receptor without hypermutated regions, and is carried out in a cell-based system using immature B cells which are in the pro/pre stage and cause a ‘Triple Knockout’ of the genes for RAG2 or RAG1, Lambda5, and SLP65.