A5103024997- T-cell and B-cell Immunology
- Immune Cell Function and Interaction
- Monoclonal and Polyclonal Antibodies Research
- Immunotherapy and Immune Responses
- Immunodeficiency and Autoimmune Disorders
- Bone Metabolism and Diseases
- Bone health and treatments
- Immune cells in cancer
- Systemic Lupus Erythematosus Research
- Folate and B Vitamins Research
- Glycosylation and Glycoproteins Research
- Pancreatitis Pathology and Treatment
- RNA and protein synthesis mechanisms
- Genomics and Phylogenetic Studies
- Respiratory viral infections research
- Viral Infectious Diseases and Gene Expression in Insects
- Immune Response and Inflammation
- Neuroscience of respiration and sleep
- Pregnancy and preeclampsia studies
- Galectins and Cancer Biology
- Autoimmune Bullous Skin Diseases
- Pancreatic and Hepatic Oncology Research
- CAR-T cell therapy research
- Acute Lymphoblastic Leukemia research
- Diabetes and associated disorders
University of Alabama at Birmingham
2014-2024
Western Michigan University
2023
Stryker (United States)
2023
National Water Research Center
2007-2020
Recent reports linking Down syndrome (DS) to maternal polymorphisms at the methylenetetrahydrofolate reductase ( MTHFR ) gene locus have generated great interest among investigators in field. The present study aimed evaluation of 677C/T and 1298A/C as risk factors for DS. Forty two mothers proven DS outcomes forty eight control with normal offspring were included. Complete medical nutritional histories all taken special emphasis on folate intake. Folic acid intake from food or vitamin...
The VpreB component of the surrogate light chain serves as an invariant antigen that may affect repertoire antibody responses.
The initiation and elongation stages of translation are directed by codon–anticodon interactions. In contrast, a release factor protein mediates stop codon recognition prior to polypeptide chain release. Previous studies have identified specific regions eukaryotic one (eRF1) that important for decoding each codon. cavity model suggests three binding pockets/cavities located on the surface eRF1's domain key elements in recognition. Thus, predicts amino acid changes or near these cavities...
Variability in the developing antibody repertoire is focused on third complementarity determining region of H chain (CDR-H3), which lies at center antigen binding site where it often plays a decisive role binding. The power VDJ recombination and N nucleotide addition has led to common conception that sequence CDR-H3 unrestricted its variability random composition. Under this view, immune response solely controlled by somatic positive negative clonal selection mechanisms act individual B...
To test whether mechanisms controlling the range of diversity developing antibody repertoire in C57BL/6 mice (IgH(b)) operate similarly to those identified BALB/c (IgH(a)), we compared sequences VH 7183-containing H-chain transcripts from sorted adult bone marrow B-cell subsets with previously obtained mice. Patterns VDJ gene segment utilization and CDR-H3 amino acid composition, charge, average length pro-B cells were similar, although not identical, cells. However, mature, recirculating B...
B-1a cells produce ‘natural’ antibodies (Abs) to neutralize pathogens and clear neo self-antigens, but the fundamental selection mechanisms that shape their polyreactive repertoires are poorly understood. Here, we identified a B cell progenitor subset defined by Fc receptor-like 6 (FCRL6) expression, harboring innate-like defense, migration, differentiation properties conducive for natural Ab generation. Compared FCRL6- pro cells, repressed mitotic, DNA damage repair, signaling activity of...
In the bone marrow, preB cells are found adjacent to endosteum where synthesizing osteoblast and resorbing osteoclasts reside. Although there is evidence of interactions between cells, factors that contribute such poorly understood. A critical checkpoint for cell development assesses integrity nascent immunoglobulin μ heavy chain (HC) by testing whether it can participate in formation a receptor (preBCR), composed HC surrogate light (LC). this work we tested loss preBCR components affect...
Sequential developmental checkpoints are used to 'optimize' the B cell antigen receptor repertoire by minimizing production of autoreactive or useless immunoglobulins and enriching for potentially protective antibodies. The first apparently most impactful checkpoint requires µHC form a functional preBCR associating with surrogate light chain, which is composed VpreB λ5. Absence any components causes block in development that characterized severe immature lymphopenia. Previously, we showed...
Systemic lupus erythematosus (SLE) is an autoimmune disease that reflects a failure to block the production of self-reactive antibodies, especially those bind double-stranded DNA (dsDNA). Backcrossing lupus-prone NZM2410 genome onto C57BL/6 led identification three genomic intervals, termed sle1, sle2 and sle3, which are associated with susceptibility. We previously generated strain congenic for immunoglobulin DH locus (ΔD–iD) enriches arginine at dsDNA-binding positions. individually...
The early B cell protein λ5 is an essential component of the surrogate light chain and preB receptor (preBCR), which critical for optimal development. To investigate effect and/or cells on bone acquisition over time, we developed a panel JH -/- , λ5-/-, wild-type (WT) BALB/c mice then studied postnatal development aging in these at one, six, twelve, twenty-two months age. trabecular volume total (BV/TV) was similar to WT all ages. In contrast, six age thereafter, λ5-/- demonstrated severe...
We have previously shown that the sequence of immunoglobulin diversity gene segment (D H ) helps dictate structure and composition complementarity determining region 3 heavy chain (CDR-H3). In order to test role germline D on preimmune TCRβ repertoire T cells, we generated a mouse with mutant DJC locus wherein Dβ2-Jβ2 cluster was deleted remaining segment, Dβ1 (IMGT:TRDB1), replaced DSP2.3 (IMGT:IGHD2-02), commonly used B cell segment. Crystallographic studies length thus TCR CDR-B3 places...
Enrichment for tyrosine in immunoglobulin CDR-H3 is due large part to natural selection of germline DH sequence. We have previously shown that when sequence modified reduce the contribution codons, epitope recognition altered and B cell development, antibody production, autoantibody morbidity mortality following pathogen challenge are adversely affected. TCRβ diversity (Dβ) gene segment sequences even more highly conserved than DH, with trout Dβ1 identical human mouse Dβ1. hypothesized Dβ...
Abstract Successive checkpoints in B cell development including differentiation the bone marrow and peripheral lymphoid organs control composition reactivity of antibody repertoire. One first key is testing efficiency heavy chain (HC) by forming a pre receptor (pre BCR) composed newly generated μHCs invariant surrogate light chains. Similar to mouse, human cells with highly charged or hydrophobic antigen binding sites are rare mature Suppression mouse reflects, part, reduced use RF2 due Dμ...
Abstract Human B cell repertoire selection depends on the composition of complementary determining heavy chain (CDR-H3), which lies at center antigen binding site. During development, preB cells express a receptor (preBCR), is composed μH bound to surrogate light (SLC). In mouse, VpreB R 101D 57R 51motif SLC selects against chains with hydrophobic CDR-H3s. Abnormal preBCR stage predisposes autoreactive survival and leukemia. We sought study in healthy human individuals versus acute...
Abstract Expression of CD19 on B cells modulates cell receptor signaling threshold. Reduced expression has been observed in some human patients with common variable immune deficiency (CVID), a disease which is characterized by low production mature paradoxical increase auto-reactivity. Development the repertoire absence not well characterized. We previously showed that controlled sequence characteristics complementary determining region heavy chain (CDR-H3). sought to examine CDR-H3 mice...