Ig Light Chain Precedes Heavy Chain Gene Rearrangement during Development of B Cells in Swine

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F17%3A00473832" target="_blank" >RIV/61388971:_____/17:00473832 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.4049/jimmunol.1601035" target="_blank" >http://dx.doi.org/10.4049/jimmunol.1601035</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4049/jimmunol.1601035" target="_blank" >10.4049/jimmunol.1601035</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Ig Light Chain Precedes Heavy Chain Gene Rearrangement during Development of B Cells in Swine

Popis výsledku v původním jazyce

The current mammalian paradigm states that 1) rearrangements in the IgH locus precede those in IgL loci, 2) IgL lambda genes rearrange only when IgL kappa genes are consumed, and 3) the surrogate L chain is necessary for selection of productive IgH gene rearrangements. We show in swine that IgL rearrangements precede IgH gene rearrangements, resulting in the expression of naked IgL on a surface of precursor B cells. Findings also suggest that there is no dependency on the surrogate L chain, and thus the authentic IgL proteins may be used for selection of the IgH repertoire. Although rearrangement starts with IgL kappa genes, it is rapidly replaced by IgL lambda rearrangement. Fast replacement is characterized by occurrence of IgL lambda(1o) IgL kappa(1o) dual-expressing precursors in which IgL kappa expression is a remnant of a previous translation. Most IgL kappa(+) B cells are then generated later, indicating that there are two waves of IgL kappa synthesis in different developmental stages with IgL lambda gene rearrangements in between. In the absence of stromal cells, the stepwise order of rearrangements is blocked so that IgL lambda gene rearrangements predominate in early B cell development. To our knowledge, this is the first evidence that some mammals can use an inverted order of Ig loci rearrangement. Moreover, a situation in which the generation of BCR-bearing IgL kappa is delayed until after IgL lambda becomes the dominant isotype may help explain the extreme deviations in the IgL kappa/IgL lambda ratios among mammals.

Název v anglickém jazyce

Ig Light Chain Precedes Heavy Chain Gene Rearrangement during Development of B Cells in Swine

Popis výsledku anglicky

The current mammalian paradigm states that 1) rearrangements in the IgH locus precede those in IgL loci, 2) IgL lambda genes rearrange only when IgL kappa genes are consumed, and 3) the surrogate L chain is necessary for selection of productive IgH gene rearrangements. We show in swine that IgL rearrangements precede IgH gene rearrangements, resulting in the expression of naked IgL on a surface of precursor B cells. Findings also suggest that there is no dependency on the surrogate L chain, and thus the authentic IgL proteins may be used for selection of the IgH repertoire. Although rearrangement starts with IgL kappa genes, it is rapidly replaced by IgL lambda rearrangement. Fast replacement is characterized by occurrence of IgL lambda(1o) IgL kappa(1o) dual-expressing precursors in which IgL kappa expression is a remnant of a previous translation. Most IgL kappa(+) B cells are then generated later, indicating that there are two waves of IgL kappa synthesis in different developmental stages with IgL lambda gene rearrangements in between. In the absence of stromal cells, the stepwise order of rearrangements is blocked so that IgL lambda gene rearrangements predominate in early B cell development. To our knowledge, this is the first evidence that some mammals can use an inverted order of Ig loci rearrangement. Moreover, a situation in which the generation of BCR-bearing IgL kappa is delayed until after IgL lambda becomes the dominant isotype may help explain the extreme deviations in the IgL kappa/IgL lambda ratios among mammals.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10606 - Microbiology

Projekt

<a href="/cs/project/GA15-02274S" target="_blank" >GA15-02274S: Úloha lehkých řetězců protilátek ve vývoji prasečích B buněk</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Immunology

ISSN

0022-1767

e-ISSN

—

Svazek periodika

198

Číslo periodika v rámci svazku

4

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

10

Strana od-do

1543-1552

Kód UT WoS článku

000395898600018

EID výsledku v databázi Scopus

2-s2.0-85013384153