A balance between BCR and inhibitory receptor signaling controls plasma cell differentiation by maintaining optimal Ets1 levels (BA2P.120)

• Published in: The Journal of immunology (1950) Vol. 192; no. 1_Supplement; pp. 45 - 45.7
• Main Authors: Luo, Wei, Mayeux, Jessica, Gutierrez, Toni, Getahun, Andy, Müller, Jennifer, Tedder, Thomas, Chen, Shu-Hsia, Rickert, Robert, Nitschke, Lars, Cambier, John, Satterthwaite, Anne, Garrett-Sinha, Lee Ann
• Format: Journal Article
• Language: English
• Published: 01.05.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.45.7

Abstract Signaling through the B cell receptor (BCR) can drive B cell activation and contribute to B cell differentiation into antibody-secreting plasma cells. The positive BCR activation signal is counterbalanced by a number of membrane-localized inhibitory receptors that limit B cell activation and plasma cell differentiation. Deficiencies in these negative signaling pathways may cause autoantibody generation and autoimmune disease in both animal models and human patients. We have previously shown that the transcription factor Ets1 can restrain B cell differentiation into plasma cells. Here, we tested the roles of the BCR and inhibitory receptors in controlling the expression of Ets1 in B cells. We found that Ets1 is down regulated in B cells by BCR or TLR signaling through a pathway dependent on PI3 kinase, Btk, IKK2 and JNK. Deficiencies in inhibitory pathways, such as a loss of the tyrosine kinase Lyn, the phosphatase SHP1 or membrane receptors CD22 or Siglec-G, result in enhanced BCR signaling and decreased Ets1 expression. Restoring Ets1 expression in Lyn- or SHP1-deficient B cells inhibits their enhanced plasma cell differentiation. Our findings suggest that the maintenance of Ets1 expression is an important function of the inhibitory Lyn -- CD22/SiglecG -- SHP1 pathway in B cells.