The IgH 3' regulatory region governs μ chain transcription in mature B lymphocytes and the B cell fate.
We report that the IgH 3' regulatory region (3'RR) has no role on μ chain transcription and pre-BCR expression in B cell progenitors. In contrast, analysis of heterozygous IgH aΔ3'RR/bwt mice indicated that the 3'RR controls μ chain transcripts in mature splenocytes and impacts membrane IgM density without obvious effect on BCR signals (colocalisation with lipid rafts and phosphorylation of Erk and Akt after BCR crosslinking). Deletion of the 3'RR modulates the B cell fate to less marginal zone B cells. In conclusion, the 3'RR is dispensable for pre-BCR expression and necessary for optimal commitments toward the marginal zone B cell fate. These results reinforce the concept of a dual regulation of the IgH locus transcription and accessibility by 5' elements at immature B cell stages, and by the 3'RR as early as the resting mature B cell stage and then along further activation and differentiation.
CNRS, CRIBL, UMR 7276, Limoges, France.
Alexis
A
Saintamand
CNRS, CRIBL, UMR 7276, Limoges, France.
Pauline
P
Rouaud
CNRS, CRIBL, UMR 7276, Limoges, France.
Armand
A
Garot
CNRS, CRIBL, UMR 7276, Limoges, France.
Faten
F
Saad
CNRS, CRIBL, UMR 7276, Limoges, France.
Claire
C
Carrion
CNRS, CRIBL, UMR 7276, Limoges, France.
Christelle
C
Oblet
CNRS, CRIBL, UMR 7276, Limoges, France.|Université de Limoges, CRIBL, UMR 7276, Limoges, France.|Institut Universitaire de France, Paris, France.
Michel
M
Cogné
CNRS, CRIBL, UMR 7276, Limoges, France.
Eric
E
Pinaud
CNRS, CRIBL, UMR 7276, Limoges, France.
Yves
Y
Denizot
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012045:Regulatory Sequences, Nucleic Acid
D007143:Immunoglobulin Heavy Chains; D007148:Immunoglobulin mu-Chains
B cell fate; BCR; IgH 3’ regulatory enhancers; knock-out mice