Natural Anti-Intestinal Goblet Cell Autoantibody Production from Marginal Zone B Cells

Ichikawa, Daiju; Asano, Masanao; Shinton, Susan A.; Brill-Dashoff, Joni; Formica, Anthony M.; Velcich, Anna; Hardy, Richard R.; Hayakawa, Kyoko

doi:10.4049/jimmunol.1402383

Cited by 26 publications

(39 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This BCR recognizes the highly glycosylated Thy‐1 glycoprotein abundantly expressed on immature thymocyte membranes, including those of dying thymocytes. Generation of V H 3609μTg mice, as well as VDJ knock‐in mice, revealed generation of mature B1a cells with this ATA BCR in the presence of self‐antigen, whereas there was no B1a cell generation in the absence of Thy‐1, demonstrating for the first time that positive selection occurs in mouse B cells, as has long been recognized for T cells.…”

Section: Differences In Bcr Signal Strength Generate B Cell Subsets Pmentioning

confidence: 78%

“…The generation of anti‐thymocyte/Thy‐1 autoreactive (ATA) BCR transgenic and knock‐in mouse lines enabled us to test the important role of BCR signaling in B1a cell generation, and the differences in B cell fate arising from different levels of BCR signaling in B‐1 and B‐2 development . The unmutated ATA IgM (V H 3609/V k 21) was originally identified as a B1a cell BCR in SM/J mice that are non‐autoimmune but are known to have an elevated level of ATA IgM autoantibody in the serum .…”

Section: Differences In Bcr Signal Strength Generate B Cell Subsets Pmentioning

confidence: 99%

See 1 more Smart Citation

B cells generated by B‐1 development can progress to chronic lymphocytic leukemia

Hayakawa

Formica

Colombo

et al. 2015

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

B cells generated early during fetal/neonatal B-1 development in mice include autoreactive cells with detectable CD5 upregulation induced by B cell receptor (BCR) signaling (B1a cells). A fraction of B1a cells are maintained by self-renewal for life, with the potential risk of dysregulated growth and progression to chronic lymphocytic leukemia (CLL)/lymphoma during aging. In studies using the Eμ-hTCL1 transgenic mouse system, it became clear that this B1a subset has a higher potential than other B cell subsets for progression to CLL. We have generated several autoreactive germline BCR gene models to compare B cells generated under conditions of natural exposure to autoantigen. Analysis of the mice has been key in understanding the importance of the BCR and BCR signaling for generating different B cell subsets and for investigating the cellular origin of B-CLL.

show abstract

Section: Differences In Bcr Signal Strength Generate B Cell Subsets Pmentioning

confidence: 78%

Section: Differences In Bcr Signal Strength Generate B Cell Subsets Pmentioning

confidence: 99%

B cells generated by B‐1 development can progress to chronic lymphocytic leukemia

Hayakawa

Formica

Colombo

et al. 2015

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…Few 24E1 + cells detected in MZ B and FO B cells were 24E1 med cells (Figure 3c); single cell Igκ sequence analysis revealed that 24E1 med cells utilized different V k 9-J k junctional residues (Figure 3c). The mouse MZ B cell pool is known to contain autoreactive B cells 26, 38 , as with B1 B cells. To assess whether the MZ B cell can include the stereotyped AMyIIA BCR, a V H Q52/D/J-μ a IgH transgenic mouse line, OK44, was generated as previously described 14 (Supplementary Figure S3).…”

Section: Resultsmentioning

confidence: 99%

“…Rag1 −/− mice were used for producing ethanol-fixed frozen tissue sections, and microscope imaging was done as described previously 26, 27 . 1/100 diluted hybridoma IgM ascites (2–10 μg/ml) were incubated on tissue section slides for 90 minutes at 37°C, followed by AlexaFluor (AF) 488 anti-IgM (331.12), together with DAPI (Thermo Scientific), with or without PE-anti-CD31 (eBioscience) (30 minutes at RT).…”

Section: Methodsmentioning

confidence: 99%

Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells

et al. 2016

View full text Add to dashboard Cite

A common feature of B cell chronic lymphocytic leukemia (CLL) is chromosomal loss of 13q14, containing the miR15a/16-1 locus controlling B cell proliferation. However, CLL etiology remains unclear. CLL is an adult leukemia with an incidence that increases with advancing age. A unique feature of CLL is biased B cell antigen receptor (BCR) usage, autoreactivity with polyreactivity, and CD5 expression, all suggest a role for the BCR in driving CLL pathogenesis. Among human CLLs, BCRs autoreactive with non-muscle myosin IIA (AMyIIA) are recurrent. Here we identify an unmutated AMyIIA BCR in mouse, with distinctive CDR3 segments capable of promoting leukemogenesis. B cells with this AMyIIA BCR are generated by BCR-dependent signaling during B-1 fetal/neonatal development with CD5 induction, but not in adults. These early-generated AMyIIA B1 B cells self-renew, increase during aging, and can progress to become monoclonal B cell lymphocytosis, followed by aggressive CLL in aged mice, often with loss of a chromosomal region containing the miR15a/16-1 locus of varying length, as in human CLL. Thus, the ability to generate this defined autoreactive BCR by B1 B cells is a key predisposing step in mice, promoting progression to chronic leukemia.

show abstract

“…Early adoptive transfer studies showed that much of the circulating IgM was produced by these cells and subsequent studies using transfer of B‐1 cells into neonatal B cell‐depleted mice showed that amount to be more than 90% . Others reported that marginal zone (MZ) B cells also contribute to natural antibody production in both humans and mice …”

Section: Natural Igm Production: Two Sides To a Coinmentioning

confidence: 99%

Secreted IgM: New tricks for an old molecule

Blandino

Baumgarth

2019

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Secreted IgM (sIgM) is a multifunctional evolutionary conserved antibody that is critical for the maintenance of tissue homeostasis as well as the development of fully protective humoral responses to pathogens. Constitutive secretion of self‐ and polyreactive natural IgM, produced mainly by B‐1 cells, provides a circulating antibody that engages with autoantigens as well as invading pathogens, removing apoptotic and other cell debris and initiating strong immune responses. Pathogen‐induced IgM production by B‐1 and conventional B‐2 cells strengthens this early, passive layer of IgM‐mediated immune defense and regulates subsequent IgG production. The varied effects of secreted IgM on immune homeostasis and immune defense are facilitated through its binding to numerous different cell types via different receptors. Recent studies identified a novel function for pentameric IgM, namely as a transporter for the effector protein ″apoptosis‐inhibitor of macrophages″ (AIM/CD5L). This review aims to provide a summary of the known functions and effects of sIgM on immune homeostasis and immune defense, and its interaction with its various receptors, and to highlight the many critical immune regulatory functions of this ancient and fascinating immunoglobulin.

show abstract

Natural Anti-Intestinal Goblet Cell Autoantibody Production from Marginal Zone B Cells

Cited by 26 publications

References 42 publications

B cells generated by B‐1 development can progress to chronic lymphocytic leukemia

B cells generated by B‐1 development can progress to chronic lymphocytic leukemia

Loss of a chromosomal region with synteny to human 13q14 occurs in mouse chronic lymphocytic leukemia that originates from early-generated B-1 B cells

Secreted IgM: New tricks for an old molecule

Contact Info

Product

Resources

About