Internalization of B cell receptors in human EU12 μHC⁺ immature B cells specifically alters downstream signaling events.
It has been recognized for a long time that engagement of B cell antigen receptors (BCRs) on immature B cells or mature B cells leads to completely opposite cell fate decisions. The underlying mechanism remains unclear. Here, we show that crosslinking of BCRs on human EU12 μHC⁺ immature B cells resulted in complete internalization of cell surface BCRs. After loss of cell surface BCRs, restimulation of EU12 μHC⁺ cells showed impaired Ca²⁺ flux, delayed SYK phosphorylation, and decreased CD19 and FOXO1 phosphorylation, which differ from those in mature Daudi or Ramos B cells with partial internalization of BCRs. In contrast, sustained phosphorylation and reactivation of ERK upon restimulation were observed in the EU12 μHC⁺ cells after BCR internalization. Taken together, these results show that complete internalization of cell surface BCRs in EU12 μHC⁺ cells specifically alters the downstream signaling events, which may favor receptor editing versus cell activation.
Department of Pathology and Microbiology, University of Nebraska Medical Center, LTC 11706A, Omaha, NE 68198-7660, USA ; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Jing
J
Liu
Wanqin
W
Xie
Miles D
MD
Lange
Sang Yong
SY
Hong
Kaihong
K
Su
Zhixin
Z
Zhang
D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000276:immunology / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism; D010766:Phosphorylation / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology*; D013499:Surface Properties; D000072377:Syk Kinase
D018941:Antigens, CD19; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase