scholarly journals Immunocytochemical identification and localization of immunoglobulin A within Paneth cells of the rat small intestine.

1976 ◽  
Vol 24 (10) ◽  
pp. 1085-1092 ◽  
Author(s):  
S L Erlandsen ◽  
C B Rodning ◽  
C Montero ◽  
J A Parsons ◽  
E A Lewis ◽  
...  
Keyword(s):  
Light Chain ◽  
Cell Function ◽  
Paneth Cell ◽  
Immunoglobulin A ◽  
Cross Reactivity ◽  
Paneth Cells ◽  
Immunoglobulin Light Chain ◽  
Specific Staining ◽  
Heavy Chains ◽  
Purified Antigen

Light microscopic immunocytochemistry was used to identify Paneth cells by their lysozyme content and to detect immunoglobulin antigens within a subpopulation of these cells. Antisera specific for the heavy chains of rat or human immunoglobulin A and for immunoglobulin light chain antigens produced specific staining of rat Paneth cells. The distribution of immunoglobulin staining varied between adjacent Paneth cells in the same crypt and between Paneth cells in adjacent crypts, as well as between Paneth cell populations of different animals. No staining of rat Paneth cells was detected using antisera specific for the heavy chain of immunoglobulins G or M. The specific staining of Paneth cells for immunoglobulin A and light chain antigens was blocked by absorption of each antiserum with its respective purified antigen. Absorption of these antisera with purified rat lysozyme did not affect staining and thereby eliminated the possibility of immunologic cross-reactivity between lysozyme and immunoglobulin antigens. It is suggested, in light of current concepts of Paneth cell function, that the immunoglobulin staining of Paneth cells may reflect their ability to phagocytize immunoglobulin A-coated microorganisms or immune complexes containing immunoglobulin A.

Immunoglobulin Light Chain Repertoire in Chronic Lymphocytic Leukemia (CLL): Recognition of Subsets with “CLL-Specific” CDR3 Regions and Associations with Heavy Chains.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 769-769 ◽  
Author(s):  
Kostas Stamatopoulos ◽  
Chrysoula Belessi ◽  
Anastasia Hadzidimitriou ◽  
Evangelia Kalagiakou ◽  
Tatjana Smilevska ◽  
...  
Keyword(s):  
Light Chain ◽  
Lymphocytic Leukemia ◽  
Molecular Processes ◽  
Immunoglobulin Light Chain ◽  
Heavy Chains ◽  
Molecular Features ◽  
Gene Usage ◽  
Region Length ◽  
Unequal Length

Abstract We analyzed immunoglobulin light chain (IgLC) repertoire in a series of 253 typical, unselected CLL cases and compared CLL IgLC sequences to GenBank IgLC sequences from normal, autoreactive and neoplastic cells. The present series included 165 κ- and 88 λ-CLL cases. Twenty-three functional IGKV genes were used in IGKV-J rearrangements in κ-CLL; the most frequent genes were: 3-20/A27 (25 cases), 1-39-1D-39/O2-O12 (19 cases), 4-1/B3 (16 cases), 1-5/L12 (15 cases), 2-30/A17 (13 cases) and 1-8/L9 (10 cases). There were 55/165 unmutated sequences (33%), 44/165 sequences (27%) with 97-99,6% homology to germline and 66/165 sequences (40%) with less than 97% homology. KCDR3 region length ranged from 6–11 (median, 9) aminoacids (aa). N nucleotides (median 3, range 1–12) were detected in 85/165 rearrangements (51.5%). IGKJ3-5 gene usage was observed in 51/165 rearrangements (30%); interestingly, IGKJ3-5 genes were used in 7/8 IGKV3-11 and 4/5 IGKV1-9 rearrangements. Subsets with homologous and “CLL-specific” KCDR3 regions were identified: IGKV2-30, 5 mutated sequences with identical KCDR3 (MQGTYWPYT), 3/5 associated with IGHV4-34 utilizing heavy chains with a similar HCDR3 of 20 aa; IGKV1-39/1D-39, 3 unmutated sequences with identical KCDR3 (QQSYSTTPLT), all associated with IGHV4-39 utilizing heavy chains with a similar HCDR3 of 19 aa; IGKV1-5, 4 unmutated sequences with identical KCDR3 (QQYNSYPWT), 2/4 associated with unmutated IGHV4-39 utilizing heavy chains with a HCDR3 of unequal length. Twenty-six functional IGLV genes were used in IGLV-J rearrangements in λ-CLL; the most frequent genes were: IGLV2-8/1-2 (14 cases), 3-21/2-14 (13 cases), 2-14/1-4 and 1-44/1-16 (7 cases each). There were 24/88 unmutated sequences (27%), 33/88 sequences (37,5%) with 97-99,6% homology to germline and 31/88 sequences (35%) with less than 97% homology. LCDR3 region length ranged from 8-13 aa (median, 11). N nucleotides (median 3, range 1-15) were detected in 42/88 rearrangements (47.7%). The IGLJ1 gene was used in 18/88 rearrangements (20%); all other rearrangements used the IGLJ3*01/*02 genes. Subsets with homologous and “CLL-specific” LCDR3 regions were identified: IGLV1-44, 2 sequences with very similar LCDR3 (AAWDDSLNGP/QV), both associated with IGHV4-b utilizing heavy chains with a similar HCDR3 of 11 aa; IGLV3-21, 7 sequences all with identical LCDR3 (QVWDSGSDHPWV), 3/7 associated with IGHV3-21 utilizing heavy chains with a similar HCDR3 of 9 aa. These results document that IgLC repertoire in CLL is biased by both intrinsic molecular processes as well as selection after LC expression. Genes that have been reported to be overexpressed in the normal and autoimmune disorders were also found to be overrepresented in the CLL repertoire, often with “CLL-specific” molecular features. Finally, the existence of subgroups with homologous CDR3 regions associated with similar heavy chains provides further evidence for the role of antigen selection in CLL pathogenesis.

One siRNA pool targeting the λ constant region stops λ light-chain production and causes terminal endoplasmic reticulum stress

Blood ◽  
2014 ◽  
Vol 123 (22) ◽  
pp. 3440-3451 ◽  
Author(s):  
Ping Zhou ◽  
Xun Ma ◽  
Lakshmanan Iyer ◽  
Chakra Chaulagain ◽  
Raymond L. Comenzo
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Light Chain ◽  
Antibody Production ◽  
Plasma Cells ◽  
Light Chains ◽  
Constant Region ◽  
Immunoglobulin Light Chain ◽  
Heavy Chains ◽  
Key Points

Key PointsImmunoglobulin light-chain and antibody production by plasma cells is significantly reduced by siRNA for the light-chain constant region. In plasma cells making intact antibodies, knockdown of light chains can cause terminal ER stress because of unpaired heavy chains.

scholarly journals ULTRASTRUCTURAL IMMUNOCYTOCHEMICAL LOCALIZATION OF LYSOZYME IN THE PANETH CELLS OF MAN

1974 ◽  
Vol 22 (6) ◽  
pp. 401-413 ◽  
Author(s):  
STANLEY L. ERLANDSEN ◽  
JONATHAN A. PARSONS ◽  
THOMAS D. TAYLOR
Keyword(s):  
Paneth Cell ◽  
Ultrastructural Level ◽  
Uranyl Acetate ◽  
Paneth Cells ◽  
Rabbit Serum ◽  
Normal Rabbit Serum ◽  
Specific Staining ◽  
Secretion Granules ◽  
Normal Sheep Serum ◽  
Unlabeled Antibody

Human lysozyme was localized immunocytochemically at the ultrastructural level within Paneth cells of man by use of the unlabeled antibody enzyme method. Specific staining for lysozyme was observed over secretion granules in the apical cytoplasm, within the region of the Golgi apparatus and within some, but not all, lysosomes. No staining was observed within the cisternae of the rough endoplasmic reticulum or other cellular organelles. In control experiments comparing semiadjacent sections of the same Paneth cell, substitution of either normal rabbit serum for rabbit antihuman lysozyme antiserum (specificity control) or normal sheep serum for sheep antirabbit immunoglobulin G antiserum (method control) completely eliminated specific staining for lysozyme. The intensity of staining for lysozyme was related to both the titer and length of exposure to antilysozyme antiserum. Specific staining was obtained in tissue embedded in Araldite or Epon and was facilitated by etching with hydrogen peroxide. No staining was observed after prolonged fixation in glutaraldehyde or treatment with uranyl acetate in block.

Ordered recombination of immunoglobulin light chain genes occurs at the IGK locus but seems less strict at theIGL locus

Blood ◽  
2001 ◽  
Vol 97 (4) ◽  
pp. 1001-1008 ◽  
Author(s):  
Mirjam van der Burg ◽  
Talip Tümkaya ◽  
Marjan Boerma ◽  
Sandra de Bruin-Versteeg ◽  
Anton W. Langerak ◽  
...  
Keyword(s):  
Light Chain ◽  
Messenger Rna ◽  
Somatic Mutations ◽  
Cell Model ◽  
Complete Analysis ◽  
Immunoglobulin Light Chain ◽  
Main Determinant ◽  
Heavy Chains ◽  
Single Cell Model ◽  
Rearrangement Processes

Abstract Regulation of allelic and isotypic exclusion of human immunoglobulin (Ig) light-chain genes was studied in 113 chronic B-cell leukemias as a “single-cell” model that allowed complete analysis of each light chain allele. Our data show that monospecific Ig light chain expression is in about 90% of cases determined by ordered recombination: Igκ gene (IGK) rearrangements, followed byIGK deletions and Igλ gene (IGL) rearrangements, resulting in the presence of only one functional Ig light chain rearrangement. In about 10% (10 cases), 2 functional Ig light chain rearrangements (IGK/IGL or IGL/IGL, but not IGK/IGK) were identified. This might be explained by the fact that regulation of the ordered recombination process is not fully strict, particularly when the IGL locus is involved. Unfavorable somatic mutations followed by receptor editing might have contributed to this finding. Eight of these 10 cases indeed contained somatic mutations. In cases with 2 functional Ig light chain rearrangements, both alleles were transcribed, but monospecific Ig expression was still maintained. This suggests that in these cases allelelic exclusion is not regulated at the messenger RNA level but either at the level of translation or protein stability or via preferential pairing of Ig light and Ig heavy chains. Nevertheless, ordered rearrangement processes are the main determinant for monospecific Ig light chain expression.

Immunoglobulin light chain repertoire in chronic lymphocytic leukemia

Blood ◽  
2005 ◽  
Vol 106 (10) ◽  
pp. 3575-3583 ◽  
Author(s):  
Kostas Stamatopoulos ◽  
Chrysoula Belessi ◽  
Anastasia Hadzidimitriou ◽  
Tatjana Smilevska ◽  
Evangelia Kalagiakou ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Light Chain ◽  
Lymphocytic Leukemia ◽  
Immunoglobulin Light Chain ◽  
Neoplastic Cells ◽  
Heavy Chains ◽  
Immunoglobulin Kappa ◽  
Complementarity Determining Region ◽  
Immunoglobulin Lambda

AbstractImmunoglobulin kappa (IGK) and immunoglobulin lambda (IGL) light chain repertoire was analyzed in 276 chronic lymphocytic leukemia (CLL) cases and compared with the relevant repertoires from normal, autoreactive, and neoplastic cells. Twenty-one functional IGKV genes were used in IGKV-J rearrangements of 179 kappa-CLL cases; the most frequent genes were IGKV3-20(A27), IGKV1-39/1D-39(O2/O12), IGKV1-5(L12), IGKV4-1(B3), and IGKV2-30(A17); 90 (50.3%) of 179 IGK sequences were mutated (similarity < 98%). Twenty functional IGLV genes were used in IGLV-J rearrangements of 97 lambda-CLL cases; the most frequent genes were IGLV3-21(VL2-14), IGLV2-8(VL1-2), and IGLV2-14(VL1-4); 44 of 97 IGL sequences (45.4%) were mutated. Subsets with “CLL-biased” homologous complementarity-determining region 3 (CDR3) were identified: (1) IGKV2-30-IGKJ2, 7 sequences with homologous kappa CDR3 (KCDR3), 5 of 7 associated with homologous IGHV4-34 heavy chains; (2) IGKV1-39/1D-39-IGKJ1/4, 4 unmutated sequences with homologous KCDR3, 2 of 4 associated with homologous IGHV4-39 heavy chains; (3) IGKV1-5-IGKJ1/3, 4 sequences with homologous KCDR3, 2 of 4 associated with unmutated nonhomologous IGHV4-39 heavy chains; (4) IGLV1-44-IGLJ2/3, 2 sequences with homologous lambda CDR3 (LCDR3), associated with homologous IGHV4-b heavy chains; and (5) IGLV3-21-IGLJ2/3, 9 sequences with homologous LCDR3, 3 of 9 associated with homologous IGHV3-21 heavy chains. The existence of subsets that comprise given IGKV-J/IGLV-J domains associated with IGHV-D-J domains that display homologous CDR3 provides further evidence for the role of antigen in CLL pathogenesis.

scholarly journals The Muc2 mucin coats murine Paneth cell granules and facilitates their content release and dispersion

2018 ◽  
Vol 315 (2) ◽  
pp. G195-G205 ◽  
Author(s):  
Martin Stahl ◽  
Sarah Tremblay ◽  
Marinieve Montero ◽  
Wayne Vogl ◽  
Lijun Xia ◽  
...  
Keyword(s):  
Cell Function ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Paneth Cells ◽  
Phenotypic Differences ◽  
Cell Functions ◽  
First Time ◽  
Electron Lucent ◽  
Granule Release

Paneth cells are a key subset of secretory epithelial cells found at the base of small intestinal crypts. Unlike intestinal goblet cells, which secrete the mucin Muc2, Paneth cells are best known for producing an array of antimicrobial factors. We unexpectedly identified Muc2 staining localized around Paneth cell granules. Electron microscopy (EM) confirmed an electron lucent halo around these granules, which was lost in Paneth cells from Muc2-deficient (−/−) mice. EM and immunostaining for lysozyme revealed that Muc2−/− Paneth cells contained larger, more densely packed granules within their cytoplasm, and we detected defects in the transcription of key antimicrobial genes in the ileal tissues of Muc2−/− mice. Enteroids derived from the small intestine of wild-type and Muc2−/− mice revealed phenotypic differences in Paneth cells similar to those seen in vivo. Moreover, lysozyme-containing granule release from Muc2−/− enteroid Paneth cells was shown to be impaired. Surprisingly, Paneth cells within human ileal and duodenal tissues were found to be Muc2 negative. Thus Muc2 plays an important role in murine Paneth cells, suggesting links in function with goblet cells; however human Paneth cells lack Muc2, highlighting that caution should be applied when linking murine to human Paneth cell functions. NEW & NOTEWORTHY We demonstrate for the first time that murine Paneth cell granules possess a halo comprised of the mucin Muc2. The presence of Muc2 exerts an impact on Paneth cell granule size and number and facilitates the release and dispersal of antimicrobials into the mucus layer. Interestingly, despite the importance of Muc2 in murine Paneth cell function, our analysis of Muc2 in human intestinal tissues revealed no trace of Muc2 expression by human Paneth cells.

scholarly journals Artificial immunoglobulin light chain with potential to associate with a wide variety of immunoglobulin heavy chains

2019 ◽  
Vol 515 (3) ◽  
pp. 481-486 ◽  
Author(s):  
Hanbing Xue ◽  
Lin Sun ◽  
Hirofumi Fujimoto ◽  
Tadaki Suzuki ◽  
Yoshimasa Takahashi ◽  
...  
Keyword(s):  
Light Chain ◽  
Immunoglobulin Light Chain ◽  
Heavy Chains

scholarly journals Functional immunoglobulin light chain genes are replaced by ongoing rearrangements of germline V kappa genes to downstream J kappa segment in a murine B cell line.

1989 ◽  
Vol 170 (1) ◽  
pp. 1-13 ◽  
Author(s):  
S Levy ◽  
M J Campbell ◽  
R Levy
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Intermediate Step ◽  
Immunoglobulin Light Chain ◽  
Additional Mechanism ◽  
Heavy Chains ◽  
Cell Clones ◽  
Parental Tumor

A murine B cell lymphoma (38C13) was subjected to immunoselection with mAbs directed against the idiotypic determinants of its cell surface Ig. Variants emerged with altered Ig receptors containing identical heavy chains but different light chains. The functional light chain genes in these variants were composed of V kappa segments drawn from the V kappa Ox-1 family, which had replaced the V kappa gene expressed by the parental tumor by rearranging to downstream J kappa segments. Rearrangement at the kappa locus continued to occur spontaneously, giving rise to secondary and tertiary variants at a rate of 1.9 x 10(-4) per cell per generation. Variants were isolated that had ceased production of surface Ig but went on to rearrange again and to become surface Ig+. The Ig- state may be an intermediate step providing a stimulus for continued rearrangement. This process provides an additional mechanism for generating diversity within B cell clones and expands the use of the available repertoire of Ig genes.

scholarly journals Crohn's disease-derived monocytes fail to induce Paneth cell defensins

2015 ◽  
Vol 112 (45) ◽  
pp. 14000-14005 ◽  
Author(s):  
Lioba F. Courth ◽  
Maureen J. Ostaff ◽  
Daniela Mailänder-Sánchez ◽  
Nisar P. Malek ◽  
Eduard F. Stange ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Mononuclear Cells ◽  
Cell Function ◽  
Paneth Cell ◽  
Constitutive Expression ◽  
Paneth Cells ◽  
Intestinal Epithelial ◽  
Peripheral Blood Mononuclear ◽  
Wnt Ligands

Crohn’s disease (CD) is associated with a multitude of genetic defects, many of which likely affect Paneth cell function. Paneth cells reside in the small intestine and produce antimicrobial peptides essential for the host barrier, principally human α-defensin 5 (HD5) and HD6. Patients with CD of the ileum are characterized by reduced constitutive expression of these peptides and, accordingly, compromised antimicrobial barrier function. Here, we present a previously unidentified regulatory mechanism of Paneth cell defensins. Using cultures of human ileal tissue, we showed that the secretome of peripheral blood mononuclear cells (PBMCs) from healthy controls restored the attenuated Paneth cell α-defensin expression characteristic of patients with ileal CD. Analysis of the Wnt pathway in both cultured biopsies and intestinal epithelial cells implicated Wnt ligands driving the PBMC effect, whereas various tested cytokines were ineffective. We further detected another defect in patients with ileal CD, because the PBMC secretomes derived from patients with CD were unable to restore the reduced HD5/HD6 expression. Accordingly, analysis of PBMC subtypes showed that monocytes of patients with CD express significantly lower levels of canonical Wnt ligands, including Wnt3, Wnt3a, Wnt1, and wntless Wnt ligand secretion mediator (Evi/Wls). These studies reveal an important cross-talk between bone marrow-derived cells and epithelial secretory Paneth cells. Defective Paneth cell-mediated innate immunity due to inadequate Wnt ligand stimulation by monocytes provides an additional mechanism in CD. Because defects of Paneth cell function stemming from various etiologies are overcome by Wnt ligands, this mechanism is a potential therapeutic target for this disease.

scholarly journals Regulation of Paneth Cell Function by RNA-Binding Proteins and Noncoding RNAs

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 2107
Author(s):  
Hee K. Chung ◽  
Lan Xiao ◽  
Krishna C. Jaladanki ◽  
Jian-Ying Wang
Keyword(s):  
Bacterial Infection ◽  
Binding Proteins ◽  
Rna Binding ◽  
Cell Function ◽  
Rna Binding Proteins ◽  
Focal Point ◽  
Paneth Cell ◽  
Noncoding Rnas ◽  
Paneth Cells ◽  
Mucosal Inflammation

Paneth cells are specialized intestinal epithelial cells that are located at the base of small intestinal crypts and play a vital role in preserving the gut epithelium homeostasis. Paneth cells act as a safeguard from bacterial translocation across the epithelium and constitute the niche for intestinal stem cells in the small intestine by providing multiple niche signals. Recently, Paneth cells have become the focal point of investigations defining the mechanisms underlying the epithelium-microbiome interactions and pathogenesis of chronic gut mucosal inflammation and bacterial infection. Function of Paneth cells is tightly regulated by numerous factors at different levels, while Paneth cell defects have been widely documented in various gut mucosal diseases in humans. The post-transcription events, specific change in mRNA stability and translation by RNA-binding proteins (RBPs) and noncoding RNAs (ncRNAs) are implicated in many aspects of gut mucosal physiology by modulating Paneth cell function. Deregulation of RBPs and ncRNAs and subsequent Paneth cell defects are identified as crucial elements of gut mucosal pathologies. Here, we overview the posttranscriptional regulation of Paneth cells by RBPs and ncRNAs, with a particular focus on the increasing evidence of RBP HuR and long ncRNA H19 in this process. We also discuss the involvement of Paneth cell dysfunction in altered susceptibility of the intestinal epithelium to chronic inflammation and bacterial infection following disrupted expression of HuR and H19.

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