Light chain editors of anti-DNA receptors in human B cells

Kalinina, Olga; Wang, Yue; Sia, Jonathan Kevin; Radic, Marko; Cazenave, Pierre‐André; Weigert, Martin

doi:10.1084/jem.20122340

Cited by 11 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since lambda CDR-L3 regions had a lower mean pI and higher acidic amino acid usage than kappa (Figure 1 ), the aforementioned ability of lambda light chains to rescue polyspecific antibodies may be a result of this charge-related phenotype. Light chains with a low CDR pI, or high aspartic acid usage, have been shown to be good at rescuing DNA-reactive heavy chains ( 47 , 48 ). This may be because DNA has a high negative charge; so, reducing the positive charge of an antibody by changing the light chain for one with more acidic character could help abolish inappropriate ionic interactions.…”

Section: Discussionmentioning

confidence: 99%

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

Townsend

Laffy

et al. 2016

Front. Immunol.

View full text Add to dashboard Cite

Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

Townsend

Laffy

et al. 2016

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…This is mainly because of an inability to distinguish human autoreactive B cells within the total B cell population. Some studies investigating receptor editing in human B cells have only been able to assess this process indirectly ( Wardemann et al, 2004 ; Schoettler et al, 2012 ; Kalinina et al, 2014 ). In other studies, differential levels of recombining sequence rearrangements and of distal Jκ usage in peripheral human B cell populations ( Lee et al, 2000 ; Ng et al, 2004 ; Panigrahi et al, 2008 ) have provided stronger support to the presence of receptor editing, but these findings have been highly correlative and did not exclude that a selective process was responsible for the observed repertoires.…”

Section: Discussionmentioning

confidence: 99%

Receptor editing and genetic variability in human autoreactive B cells

Lang

Ota

Kelly

et al. 2015

Journal of Experimental Medicine

View full text Add to dashboard Cite

show abstract

“…Though, it is formally possible that ASC derived from autoreactive VH4–34 memory cells might not differentiate into LLPC, thereby diminishing their pathogenic significance. Alternatively, it is also possible that autoreactive VH4–34 memory clones may have been redeemed by light chain editors, where certain light chains modify binding properties of the heavy chain (67, 68), or the use of particular HCDR3s. Ultimately, the contribution of different mechanisms to prevent VH4–34-mediated autoimmunity will have to be assessed by high-throughput analysis of single memory cells and PC obtained from peripheral and BM compartments.…”

Section: Selection Of Vh4–34-encoded Autoantibodies In Slementioning

confidence: 99%

“…This feature would explain the elimination of a fraction of 9G4 antibodies shortly after treatment with rituximab. 63,64 Given its clinical relevance, the analysis of the VH4-34 repertoire represents a powerful experimental system for the study of 67,68 or the use of particular HCDR3s. Ultimately, the contribution of different mechanisms to prevent VH4-34-mediated autoimmunity will have to be assessed by high-throughput analysis of single memory cells and PC obtained from peripheral and BM compartments.…”

Section: S Elec Ti On Of Vh4 -3 4 -En Coded Autoantibod Ie S In S Lementioning

confidence: 99%

Understanding B‐cell activation and autoantibody repertoire selection in systemic lupus erythematosus: A B‐cell immunomics approach

Tipton

Hom

Fucile

et al. 2018

Immunological Reviews

View full text Add to dashboard Cite

Understanding antibody repertoires and in particular, the properties and fates of B cells expressing potentially pathogenic antibodies is critical to define the mechanisms underlying multiple immunological diseases including autoimmune and allergic conditions as well as transplant rejection. Moreover, an integrated knowledge of the antibody repertoires expressed by B cells and plasma cells (PC) of different functional properties and longevity is essential to develop new therapeutic strategies, better biomarkers for disease segmentation, and new assays to measure restoration of B-cell tolerance or, at least, of normal B-cell homeostasis. Reaching these goals, however, will require a more precise phenotypic, functional and molecular definition of B-cell and PC populations, and a comprehensive analysis of the antigenic reactivity of the antibodies they express. While traditionally hampered by technical and ethical limitations in human experimentation, new technological advances currently enable investigators to address these questions in a comprehensive fashion. In this review, we shall discuss these concepts as they apply to the study of Systemic Lupus Erythematosus.

show abstract

Light chain editors of anti-DNA receptors in human B cells

Abstract: Human L chain repertoire includes editor L chains that appear to regulate anti-DNA B cells and shape the B cell repertoire.

Cited by 11 publications

References 34 publications

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions

Receptor editing and genetic variability in human autoreactive B cells

Understanding B‐cell activation and autoantibody repertoire selection in systemic lupus erythematosus: A B‐cell immunomics approach

Contact Info

Product

Resources

About