Id2 negatively regulates B cell differentiation in the spleen.
Early stages of B cell development occur in the bone marrow, resulting in formation of immature B cells. These immature cells migrate to the spleen where they differentiate into mature (B2 or marginal zone (MZ)) cells. This final maturation step is crucial for B cells to become responsive to Ags and to participate in the immune response. Id2 is a helix-loop-helix protein that lacks a DNA-binding region; and therefore, inhibits basic helix-loop-helix functions in a dominant negative manner. In this study, we show that Id2 expression is down-regulated during differentiation of immature B cells into mature B2 and MZ B cells. The high levels of Id2 expressed in the immature B cells result in inhibition of E2A binding activity to an E2 box site. Moreover, mice lacking Id2 show an elevation in the proportion of mature B2 cells in the spleen, while the MZ population in these mice is almost absent. Thus, Id2 acts as a regulator of the differentiation of immature B cells occurring in the spleen, it negatively controls differentiation into mature B2 cells while allowing the commitment to MZ B cells. In the absence of Id2 control, the unregulated differentiation is directed toward the mature B2 population.
Becker-Herman
Shirly
S
Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel.
Lantner
Frida
F
Shachar
Idit
I
D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins; D002454:Cell Differentiation; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D051797:Inhibitor of Differentiation Protein 2; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins; D013154:Spleen / Q000276:immunology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic
D051792:Basic Helix-Loop-Helix Proteins; D004247:DNA; D004268:DNA-Binding Proteins; D051797:Inhibitor of Differentiation Protein 2; D012097:Repressor Proteins; D014157:Transcription Factors; C497452:Idb2 protein, mouse; C407909:TCF3 protein, human