Receptor editing and marginal zone B cell development are regulated by the helix-loop-helix protein, E2A.
Previous studies have indicated that the E2A gene products are required to initiate B lineage development. Here, we demonstrate that E2A(+/-) B cells that express an autoreactive B cell receptor fail to mature due in part to an inability to activate secondary immunoglobulin (Ig) light chain gene rearrangement. Both RAG1/2 gene expression and RS deletion are severely defective in E2A(+/-) mice. Additionally, we demonstrate that E2A(+/-) mice show an increase in the proportion of marginal zone B cells with a concomitant decrease in the proportion of follicular B cells. In contrast, Id3-deficient splenocytes show a decline in the proportion of marginal zone B cells. Based on these observations, we propose that E-protein activity regulates secondary Ig gene rearrangement at the immature B cell stage and contributes to cell fate determination of marginal zone B cells. Additionally, we propose a model in which E-proteins enforce the developmental checkpoint at the immature B cell stage.
Quong
Melanie W
MW
Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Martensson
Annica
A
Langerak
Anton W
AW
Rivera
Richard R
RR
Nemazee
David
D
Murre
Cornelis
C
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D001483:Base Sequence; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D016654:Genes, RAG-1; D018257:Helix-Loop-Helix Motifs; D006579:Heterozygote; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017393:RNA Editing; D011947:Receptors, Antigen, B-Cell / Q000235:genetics*; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D051792:Basic Helix-Loop-Helix Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011947:Receptors, Antigen, B-Cell; D051820:TCF Transcription Factors; D058125:Transcription Factor 7-Like 1 Protein; D014157:Transcription Factors; C075668:Tcf3 protein, mouse; C544913:Tcf7l1 protein, mouse