Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized a proliferation-inducing ligand gene. Non-human animals and cells that express a human or humanized a proliferation-inducing ligand protein from an endogenous a proliferation-inducing ligand locus are described.

In one aspect, the invention provides methods of inhibiting the effects of MASP-2-dependent complement activation in a human subject suffering from graft-versus-host disease and/or diffuse alveolar hemorrhage and/or veno-occlusive disease associated with a hematopoietic stem cell transplant. The methods comprise the step of administering, to a subject in need thereof, an amount of a MASP-2 inhibitory agent effective to inhibit MASP-2-dependent complement activation.

Provided herein are methods and materials for treating autoimmune diseases and alloimmune diseases. Specifically, provided are a pharmaceutical composition comprising a therapeutically effective amount of a population of modified human T cells, wherein the human T cells are modified to comprise a nucleic acid sequence that encodes a chimeric antigen receptor (CAR) construct, wherein the CAR construct comprises an antigen binding domain, wherein the antigen binding domain is specific for a ligand expressed on B cells, plasma cells or plasmablasts in human patients suffering from an autoimmune disease or an alloimmune disease; and a method of treating an autoimmune or an alloimmune disease in a human patient, the method comprising: administering a pharmaceutical composition.

Method and compositions for modulating specific populations of monocytes or macrophages are disclosed. Methods include, in certain embodiments, modulating expression or activity of Nr4a1 (Nur77). Compositions disclosed herein include agonistic and antagonistic agents that modulate expression or activity of Nur77 and uses thereof. In various embodiments, methods of treating certain disorders and diseases related to aberrant monocyte or macrophage development are provided. In further various embodiments, methods of identifying agents that modulate specific populations of monocytes or macrophages, and agents that modulate Nur77 activity and/or expression are provided.

The present invention relates to an interleukin-2 receptor gamma (IL2RG) gene-targeting vector, a method for producing an immune cell-deficient transgenic cloned miniature pig having the vector introduced therein, and the use thereof.

An sortase-mediated intercellular labeling method allowing for tracking ligand-receptor interaction both in vitro and in vivo; and uses thereof for tracking molecule interactions both in vitro and in vivo, identifying modulators of ligand-receptor interaction, identifying potential binding partners of a protein of interest, identifying B cells expressing high affinity B cell receptors to antigens, and identifying the antigen to which a T cell of interest binds.

The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I polypeptide and/or human or humanized 2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Methods and compositions are provided for modifying one or more target loci in a cell. Such methods comprise providing a cell comprising a first polynucleotide encoding a first selection marker operably linked to a first promoter active in the cell, wherein the first polynucleotide further comprises a first recognition site for a first nuclease agent. A first nuclease agent is introduced into a cell, wherein the first nuclease agent induces a nick or double-strand break at the first recognition site. Further introduced into the cell is a first targeting vector comprising a first insert polynucleotide flanked by a first and a second homology arm that correspond to a first and a second target site located in sufficient proximity to the first recognition site. At least one cell is then identified comprising in its genome the first insert polynucleotide integrated at the target locus.

Non-human animals, cells, methods and compositions for making and using the same are provided, wherein the non-human animals and cells comprise a humanized B-cell activating factor gene. Non-human animals and cells that express a human or humanized B-cell activating factor protein from an endogenous B-cell activating factor locus are described.

The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.