Regulation of the BCR signalosome by the class II peptide editor, H2-M, affects the development and repertoire of innate-like B cells.

The non-classical Major Histocompatibility Complex class II (MHCII) protein, H2-M, edits peptides bound to conventional MHCII in favor of stable peptide/MHCII (p/MHCII) complexes. Here, we show that H2-M deficiency affects B-1 cell survival, reduces cell renewal capacity, and alters immunoglobulin repertoire, allowing for the selection of cells specific for highly abundant epitopes, but not low-frequency epitopes. H2-M-deficient B-1 cells have shorter CDR3 length, higher content of positively charged amino acids, shorter junctional regions, less mutation frequency, and a skewed clonal distribution.

Hematopoietic Stem Cell Requirement for Macrophage Regeneration Is Tissue Specific.

Tissue-resident macrophages (TRMΦ) are important immune sentinels responsible for maintaining tissue and immune homeostasis within their specific niche. Recently, the origins of TRMΦ have undergone intense scrutiny, in which now most TRMΦ are thought to originate early during embryonic development independent of hematopoietic stem cells (HSCs). We previously characterized two distinct subsets of mouse peritoneal cavity macrophages (MΦ) (large and small peritoneal MΦ) whose origins and relationship to both fetal and adult long-term (LT) HSCs have not been fully investigated.

Ultra-selective carbon nanotubes for photoacoustic imaging of inflamed atherosclerotic plaques.

Disruption of vulnerable atherosclerotic plaques often leads to myocardial infarction and stroke, the leading causes of morbidity and mortality in the United States. A diagnostic method that detects high-risk atherosclerotic plaques at early stages could prevent these sequelae. The abundance of immune cells in the arterial wall, especially inflammatory Ly-6C monocytes and foamy macrophages, is indicative of plaque‎ inflammation, and may be associated with plaque vulnerability.

IL-6 signaling mediates the germinal center response, IgM production and nociceptive sensitization in male mice after tibia fracture.

Background: Up-regulated interleukin 6 (IL-6) signaling, immune system activation, and pronociceptive autoantibodies are characteristic of complex regional pain syndrome (CRPS). IL-6 is known to promote B cell differentiation, thus we hypothesized that IL-6 signaling plays a crucial role in the development of adaptive immune responses and nociceptive sensitization in a murine tibia fracture model of CRPS.

Methods: Mice deficient in IL-6 expression (IL-6) or B cell deficient (muMT) underwent tibia fracture and 3 weeks of cast immobilization or sham injury.

CTLA-4 expression by B-1a B cells is essential for immune tolerance.

CTLA-4 is an important regulator of T-cell function. Here, we report that expression of this immune-regulator in mouse B-1a cells has a critical function in maintaining self-tolerance by regulating these early-developing B cells that express a repertoire enriched for auto-reactivity. Selective deletion of CTLA-4 from B cells results in mice that spontaneously develop autoantibodies, T follicular helper (Tfh) cells and germinal centers (GCs) in the spleen, and autoimmune pathology later in life.