Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions

Wang, Hongsheng; Shin, Dong‐Mi; Abbasi, Sadia; Jain, Shweta; Kovalchuk, Alexander L.; Beaty, Natalie; Chen, Sophia; González-Garcı́a, Inés; Morse, Herbert C.

doi:10.1073/pnas.1212428109

Cited by 37 publications

(65 citation statements)

References 65 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Rather, CD73 identifies a specific CD73 hi subset that differs little from CD73 − B-1 cells in many functional parameters with the notable exception of ectoezyme activity. However, CD73 expression is not the only surface antigen that distinguishes B-1 cell subpopulations, as B-1 cell phenotypic heterogeneity extends to expression of PD-L2 (45), CD80 (61), CD25 (47), PC1 (48) and CD5 (42). Interestingly, Shlomchik’s group recently reported that CD73, PD-L2 and CD80 are expressed by some memory B (Bmem) cells, suggesting that Bmem cells are phenotypically heterogeneous (50, 51), much like B-1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…B-1a cells are the primary source of natural antibody which can also be contributed by marginal zone B cells whereas B-1b cells contribute long lasting memory to some kinds of bacteria or virus infections (43) (44). In addition to CD5, recent studies have revealed that B-1 cell populations can be subdivided based on the expression of PD-L2 (CD273) (45, 46), CD25 (47) and PC1 (also termed ENPP1) (48). It was originally reported that CD73 is expressed on a few mouse splenic B cells (49) and more recent data show that CD73 is expressed by memory B (Bmem) cells (50, 51).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A Novel Mechanism of B Cell–Mediated Immune Suppression through CD73 Expression and Adenosine Production

Kaku

Cheng

Al‐Abed

et al. 2014

The Journal of Immunology

109

103

View full text Add to dashboard Cite

Immune suppression by regulatory T (Treg) cells and regulatory B (Breg) cells is a critical mechanism to limit excess inflammation and autoimmunity. IL-10 is considered to be the major mediator of B cell-induced immune suppression. Here, we report a novel mechanism for immune suppression through adenosine generation by B cells. We identified a novel population of B cells that expresses CD73 as well as CD39, two ecto-enzymes that together catalyze the extracellular dephosphorylation of adenine nucleotides to adenosine. Whereas CD39 expression is common among B cells, CD73 expression is not. Approximately 30–50% of B-1 cells (B220+CD23−) and IL-10 producing B (B10) cells (B220+CD5+CD1dhi) are CD73hi, depending on mouse strain, whereas few conventional B-2 cells (B220+CD23+AA4.1−) express CD73. In keeping with expression of both CD73 and CD39, we found that CD73+ B cells produce adenosine in the presence of substrate whereas B-2 cells don’t. CD73−/− mice were more susceptible to dextran sulfate sodium salt (DSS)-induced colitis than wild type (WT) mice, and transfer of CD73+ B cells ameliorated the severity of colitis, suggesting that B cell CD73/CD39/adenosine can modulate DSS-induced colitis. IL-10 production by B cells is not affected by CD73-deficiency. Interestingly, adenosine generation by IL-10−/− B cells is impaired due to reduced expression of CD73, indicating an unexpected connection between IL-10 and adenosine and suggesting caution in interpreting the results of studies with IL-10−/− cells. Together our findings demonstrate a novel regulatory role of B cells on colitis through adenosine generation in an IL-10-independent manner.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A Novel Mechanism of B Cell–Mediated Immune Suppression through CD73 Expression and Adenosine Production

Kaku

Cheng

Al‐Abed

et al. 2014

The Journal of Immunology

109

103

View full text Add to dashboard Cite

show abstract

“…The two classic functions of B-1a cells, i) innate-like and ii) immunoregulatory can be segregated between two unique subsets based on the expression of plasma cell alloantigen 1 (PC1), also known as ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), an enzyme involved primarily in the hydrolysis of ATP at the cell surface [59]. These subsets, designated B-1a.PC1 lo and B-1a.PC1 hi , express distinct IgH repertoires and contribute to varied levels of serum and mucosal natural Abs [59].…”

Section: B-1-related Cells and Subsets In Innate Immunitymentioning

confidence: 99%

The role of B-1 cells in inflammation

et al. 2015

View full text Add to dashboard Cite

B-1 lymphocytes exhibit unique phenotypic, ontogenic, and functional characteristics that differ from the conventional B-2 cells. B-1 cells spontaneously secrete germline-like, repertoire skewed polyreactive natural antibody, which acts as a first line of defense by neutralizing a wide range of pathogens before launching of the adaptive immune response. Immunomodulatory molecules, such as interleukin-10 (IL-10), adenosine, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, and IL-35 are also produced by B-1 cells in the presence or absence of stimulation, which regulate acute and chronic inflammatory diseases. Considerable progress has been made during the past three decades since the discovery of B-1 cells, which has not only improved our understanding of their phenotypic and ontogenic uniqueness but also their role in various inflammatory diseases including influenza, pneumonia, sepsis, atherosclerosis, inflammatory bowel disease (IBD), autoimmunity, obesity and diabetes mellitus. Recent identification of human B-1 cells widens the scope of this field, leading to novel innovations that can be implemented from bench to bedside. Among the vast number of studies on B-1 cells, we have carried out a literature review highlighting current trends in the study of B-1 cell involvement during inflammation, which may result in a paradigm shift towards sustainable therapeutics in various inflammatory diseases.

show abstract

“…reactive B cells versus regulatory B cells, and in the role that each of these subsets play at different stages of disease progression. While B effector cells seem to contribute to disease progression, regulatory B cells may be protective against disease initiation, including IL-10 producing B-cells [95]. …”

Section: 0 Near Future: the Immune Networkmentioning

confidence: 99%

Advances in pharmacotherapy for primary biliary cirrhosis

Mousa

Lleo

Invernizzi

et al. 2014

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction Primary Biliary Cirrhosis (PBC) is a chronic autoimmune liver disease mostly seen in middle aged women characterized by progressive non-suppurative destruction of small bile ducts resulting in intrahepatic cholestasis, parenchymal injury, and ultimately end stage liver disease. Despite major breakthroughs in our understanding of PBC, there remains only one FDA-approved agent for treatment: ursodeoxycholic acid (UDCA) to which one third of patients are unresponsive. Areas covered Biochemical response to treatment with UDCA is associated with excellent survival rates in PBC patients. However, there is a need for alternative treatments for non-responders. Results from human epidemiological and genetic studies as well as preclinical studies in PBC animal models have provided a strong impetus for the development of new therapeutic agents. In this review, we discuss the recent advances in translational research in PBC focusing on promising therapeutic approaches, namely immune-based targeted therapies and agents targeting the synthesis and circulation of bile acids. Expert opinion We are in a new era for the development of novel therapies for PBC. Data on fibrates, budesonide, and obeticholic acid offer encouragement for non-responders to UDCA.

show abstract

Expression of plasma cell alloantigen 1 defines layered development of B-1a B-cell subsets with distinct innate-like functions

Cited by 37 publications

References 65 publications

A Novel Mechanism of B Cell–Mediated Immune Suppression through CD73 Expression and Adenosine Production

A Novel Mechanism of B Cell–Mediated Immune Suppression through CD73 Expression and Adenosine Production

The role of B-1 cells in inflammation

Advances in pharmacotherapy for primary biliary cirrhosis

Contact Info

Product

Resources

About