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Comparative Immunology
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
The first animals to utilize a specific adaptive immune system incorporating MHC molecules for antigen presentation, immunoglobulins, and TCRs generated by gene segment recombination are the cartilaginous fish. Subsequent evolution simply refined the process. Thus, there is a move from the early multilocus arrangement of immunoglobulin genes to the mammalian arrangement involving few C genes and multiple V genes. There are changes in the structure of immunoglobulin heavy chains and hence in the class of immunoglobulins produced by each species. Probably one of the most significant changes was the need for mammals to adapt to the immunological challenges of bearing live young and the consequent need to prevent immunological attack on the mammalian fetus.
Molecular Mechanisms Controlling Immunoglobulin E Responses
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Rachel L. Miller, Paul B. Rothman
Immunoglobulin heavy-chain class switching is the process whereby an activated B cell changes the heavy-chain constant region at the carboxy terminus (CH) of the antibody it produces to alter its effector function while still retaining its antigenic specificity. In general, Ig class switching occurs by a deletional recombination event between regions of repetitive DNA, called switch (S) regions, that are present upstream of each heavy-chain constant region, except Cδ. This recombination juxtaposes the fully assembled variable region (composed of rearranged VDJ gene segments) directly upstream of different CH genes that encode for different Ig isotypes. For example, in the case of Ig class switching from IgM to IgE, the C03BC; locus and downstream genes are deleted so that the C∈ gene becomes juxtaposed directly 3′ to the VDJ region and VDJ-C∈ transcripts are encoded [24].
Dynamics of Immunoglobulin and T-cell Receptor Genes Recombinations During Lymphocyte Development
Published in Gérard Chaouat, The Immunology of the Fetus, 2020
Daniele Primi, Evelyne Jouvin-Marche, Raphael A. Clynes, Jean-Pierre Marolleau, Carine Gris, Kenneth B. Marcu, Pierre-André Cazenave
The initial phase of ordered immunoglobulin heavy chain (IgH) gene rearrangements, namely D to J joins, are not restricted to cells committed to the B-lymphocyte lineage.33-36 We hybridized EcoRI-digested DNAs of our cell lines with a JH probe (see Figure 4) to determine if TcR gene rearrangements precede those of the Igh locus in early T-cells. All cell lines except M15T and M15S (which have each retained one JH allele in embryonic configuration) exhibit JH recombinations at both Igh alleles. M8T was exceptional in possessing three new rearranged EcoRI bands of 16, 7.5, and 5.2 kb, but the TcR rearrangements described above for M8T indicate that it is not oligoclonal. The intensity of the 16-kb fragment is lower than the 7.5-kb band. The enlarged thymus, from which this line was originally established, contained only the 16- and 7.5-kb fragments (data not shown), suggesting that the new 5.2-kb fragment arose from a secondary D-JH rearrangement. It is difficult to establish which JH allele was involved in this secondary rearrangement, since as in the M8T line, the 16-kb band intensity was also lower than the 7.5-kb species in the tissue sample (data not shown, Figure 4).
Paraproteins and electrolyte assays: exclusion effect and effect of paraprotein elimination
Published in Scandinavian Journal of Clinical and Laboratory Investigation, 2023
Tapio Lahtiharju, Eerika Lehtisyrjä, Pipsa Kulovesi, Kari Pulkki
We collected 63 surplus plasma samples from 49 different patients. The samples were gathered by finding surplus samples with concurrent high serum total protein, or high plasma immunoglobulin A or M. The collected samples were stored at −30 °C until the day of analysis. The samples were collected from February to June 2021 and analysed between June and August 2021. Only the first successfully analysed sample from each patient was used to statistical analysis. One of the patients had only polyclonal immunoglobulins and no paraproteins. Other patients had paraproteins consisting of immunoglobulin heavy chains G, A and M, and light chains kappa and lambda. Helsinki University Hospital approved the study protocol and granted the research permit. Because our study had only left-over samples and registry data, approval from the ethical committee was not needed.
Clonal heterogeneity of polymorphic B-cell lymphoproliferative disease, EBV-positive, iatrogenic/immune senescence: implications on pathogenesis and treatment
Published in Hematology, 2022
Yu-Yan Hwang, Rex Au-Yeung, Rock Y.Y. Leung, Eric Tse, Yok-Lam Kwong
Polymerase chain reaction (PCR) for immunoglobulin heavy chain, and κ and λ light chain genes (IGH, IGK, IGL) was performed. The EBV+ B-cell LPD (first nasopharyngeal biopsy) and the EBV– plasma cell lesion (second nasopharyngeal biopsy) showed identical IGH, IGK and IGL rearrangements (Figure 4). PCR for IGH in the marrow aspirate showed a clonal pattern, but the amplification peaks were weak and could not be conclusively shown to be identical with those of the nasopharyngeal biopsies. Next generation sequencing (NGS) of 35 lymphoid-relevant genes (ALK, ATM, BCL10, BCL2, BCL6, BIRC3, BTK, CARD11, CD79A, CD79B, CRKL, DNMT3A, EZH2, FBXW7, IDH1, IDH2, IRF4, JAK1, JAK2, JAK3, MALT1, MTOR, MYC, MYD88, NOTCH1, POT1, RHOA, SETD2, SF3B1, STAT3, STAT5A, STAT5B, TET2, TP53, and XPO1) was performed (Illumina MiSeq, Illumina, San Diego, CA, U.S.A.). The EBV+ B-cell LPD showed mutations in only one gene (TP53). On the other hand, the EBV– plasma cell lesion showed mutations in five different genes (TP53, SF3B1, STAT5B, CD79B and CRKL) (Table 1).
More Accurate Diagnosis of Vitreoretinal Lymphoma Using a Combination of Diagnostic Test Results: A Prospective Observational Study
Published in Ocular Immunology and Inflammation, 2022
Rie Tanaka, Toshikatsu Kaburaki, Kazuki Taoka, Ayako Karakawa, Hideki Tsuji, Masako Nishikawa, Yutaka Yatomi, Aya Shinozaki‐Ushiku, Tetsuo Ushiku, Fumiyuki Araki
In addition to the above-mentioned specific ocular findings, diagnostic vitrectomy is needed for a definitive diagnosis of VRL, and the gold standard for diagnosis is the presence of malignant lymphoma (ML) cells in vitreous, aqueous, or chorioretinal biopsy specimens. However, cytology specimens obtained at the time of vitrectomy have been shown to generate false negative results in 30%–45% of cases of VRL.6,11,12 Loss of tumor cells or damage to the tumor tissue during biopsy sometimes impairs the accuracy of cytodiagnosis,6,13,14 while administration of corticosteroids can mask the typical tumor cell characteristics.6,15 Therefore, a comprehensive approach is needed for diagnosis of VRL. Cytokine analysis, immunoglobulin heavy chain (IgH) gene rearrangement, and flow cytometry for B-cell clonality are useful supplementary diagnostic methods. Interleukin (IL)-10 is a cytokine expressed by malignant B-cells.2,14 An IL-10/IL-6 ratio >1 suggests a diagnosis of B-cell VRL.6,9,14,16 Flow cytometry can examine cell surface markers and demonstrate monoclonal B-cell populations.9,17 VRL typically comprises a monoclonal B-cell population with restricted κ or λ chains. A κ/λ ratio >3 or <0 · 5 is a highly sensitive marker of lymphoma.18 Measurement of CD19 and/or CD20 expression is also useful for detecting B-cell lymphoma,18,19 as is polymerase chain reaction for IgH gene rearrangement.2,6,20,21