B Cells Producing Pathogenic Autoantibodies

Zou, Yong-Rui; Diamond, Betty

doi:10.1016/b978-0-12-397933-9.00023-0

Cited by 3 publications

(3 citation statements)

References 223 publications

(222 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The thyroid self Ag spread due to HCV E2 engagement to CD81 receptor on thyroid cells lead to generation of autoreactive B-cells then loss of tolerance. Uncontrolled generation of TFH cells shape the outcome of autoreactive B-cells differentiation, resulting in increased production of autoantibodies, inflammation and tissue injury [32] as shown in Figure 1. Table 1: Difference in surface markers between Pre-TFH and GC-TFH.…”

Section: T Follicular Helper Cells and Autoimmune Thyroiditis (Aitd) mentioning

confidence: 99%

Role of T Follicular Helper (Tfh) Cells Plasticity in Autoimmune Thyroiditis among Hepatitis C Virus Infection

Hetta¹

2017

GHOA

View full text Add to dashboard Cite

T follicular helper (Tfh) cells are a new subset of CD4+ T cells located in tonsils and circulating in the blood. Thf cells are required for maintenance of the germinal center reactions and generation of humoral immunity via their expression of many molecules as CD40 ligand, IL-21, IL-4, and others. Tfh cells provide the help to B-cells to differentiate to plasma cells. It has a unique phenotype CXCR5+ and express a master regulator BCL-6.

show abstract

Section: T Follicular Helper Cells and Autoimmune Thyroiditis (Aitd) mentioning

confidence: 99%

Role of T Follicular Helper (Tfh) Cells Plasticity in Autoimmune Thyroiditis among Hepatitis C Virus Infection

Hetta¹

2017

GHOA

View full text Add to dashboard Cite

show abstract

“…Uncontrolled generation of TFH cells shape the outcome of autoreactive B-cells differentiation, resulting in increased production of autoantibodies, inflammation and tissue injury [32] as shown in Figure 1. …”

Section: Icosmentioning

confidence: 99%

Untitled

2017

GHOA

View full text Add to dashboard Cite

show abstract

“…ADCC is an adaptive immune response, largely mediated by natural killer (NK) cells, but also by other effector cells such as polymorphonuclear leukocytes (PMNs), and macrophages (Igietseme et al, 2014). The ADCC cytolytic mechanism is evoked through the CD16 (FCγRIII) receptor present on the NK cell surface where binding to the Fc portion of IgG antibodies occurs leading to the phosphorylation of immunoreceptor tyrosine‐based activation motifs (ITAMs), triggering signaling pathways in the effector cells, resulting in the release of cytotoxic granules containing perforin and granzymes to kill antibody‐coated tumor cells (Gómez Román et al, 2014; Jefferis, 2009; Scully & Alter, 2016; Tsokos, 2004; Zou & Diamond, 2015). Moreover, antibodies can also initiate the complement‐dependent cytotoxicity (CDC) through binding of the Fc domain to the C1q complex (Weiner et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

The interplay of protein engineering and glycoengineering to fine‐tune antibody glycosylation and its impact on effector functions

Wang

Zhang

et al. 2021

Biotech & Bioengineering

View full text Add to dashboard Cite

The N‐glycan pattern of an IgG antibody, attached at a conserved site within the fragment crystallizable (Fc) region, is a critical antibody quality attribute whose structural variability can also impact antibody function. For tailoring the Fc glycoprofile, glycoengineering in cell lines as well as Fc amino acid mutations have been applied. Multiple glycoengineered Chinese hamster ovary cell lines were generated, including defucosylated (FUT8KO), α‐2,6‐sialylated (ST6KI), and defucosylated α‐2,6‐sialylated (FUT8KOST6KI), expressing either a wild‐type anti‐CD20 IgG (WT) or phenylalanine to alanine (F241A) mutant. Matrix‐assisted laser desorption ionization‐time of flight mass spectrometry characterization of antibody N‐glycans revealed that the F241A mutation significantly increased galactosylation and sialylation content and glycan branching. Furthermore, overexpression of recombinant human α‐2,6‐sialyltransferase resulted in a predominance of α‐2,6‐sialylation rather than α‐2,3‐sialylation for both WT and heavily sialylated F241A antibody N‐glycans. Interestingly, knocking out α‐1,6‐fucosyltransferase (FUT8KO), which removed core fucose, lowered the content of N‐glycans with terminal Gal and increased levels of terminal GlcNAc and Man5 groups on WT antibody. Further complement‐dependent cytotoxicity (CDC) analysis revealed that, regardless of the production cells, WT antibody samples have higher cytotoxic CDC activity with more exposed Gal residues compared to their individual F241A mutants. However, the FUT8KO WT antibody, with a large fraction of bi‐GlcNAc structures (G0), displayed the lowest CDC activity of all WT antibody samples. Furthermore, for the F241A mutants, a higher CDC activity was observed for α‐2,6‐ compared to α‐2,3‐sialylation. Antibody‐dependent cellular cytotoxicity (ADCC) analysis revealed that the defucosylated WT and F241A mutants showed enhanced in vitro ADCC performance compared to their fucosylated counterparts, with the defucosylated WT antibodies displaying the highest overall ADCC activity, regardless of sialic acid substitution. Moreover, the FcγRIIIA receptor binding by antibodies did not always correspond directly with ADCC result. This study demonstrates that glycoengineering and protein engineering can both promote and inhibit antibody effector functions and represent practical approaches for varying glycan composition and functionalities during antibody development.

show abstract

B Cells Producing Pathogenic Autoantibodies

Cited by 3 publications

References 223 publications

Role of T Follicular Helper (Tfh) Cells Plasticity in Autoimmune Thyroiditis among Hepatitis C Virus Infection

Role of T Follicular Helper (Tfh) Cells Plasticity in Autoimmune Thyroiditis among Hepatitis C Virus Infection

Untitled

The interplay of protein engineering and glycoengineering to fine‐tune antibody glycosylation and its impact on effector functions

Contact Info

Product

Resources

About