title: B cell receptor signal strength determines B cell fate.
abstract: B cell receptor (BCR)-mediated antigen recognition is thought to regulate B cell differentiation. BCR signal strength may also influence B cell fate decisions. Here, we used the Epstein-Barr virus protein LMP2A as a constitutively active BCR surrogate to study the contribution of BCR signal strength in B cell differentiation. Mice carrying a targeted replacement of Igh by LMP2A leading to high or low expression of the LMP2A protein developed B-1 or follicular and marginal zone B cells, respectively. These data indicate that BCR signal strength, rather than antigen specificity, determines mature B cell fate. Furthermore, spontaneous germinal centers developed in gut-associated lymphoid tissue of LMP2A mice, indicating that microbial antigens can promote germinal centers independently of BCR-mediated antigen recognition.
authors.affiliation: CBR Institute for Biomedical Research, Harvard Medical School, Boston, MA 02115, USA. casola@cbr.med.harvard.edu
authors.forename: Stefano
authors.initials: S
authors.lastname: Casola
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Otipoby
authors.forename: Marat
authors.initials: M
authors.lastname: Alimzhanov
authors.forename: Sibille
authors.initials: S
authors.lastname: Humme
authors.forename: Nathalie
authors.initials: N
authors.lastname: Uyttersprot
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Michael C
authors.initials: MC
authors.lastname: Carroll
authors.forename: Klaus
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004064:Digestive System / Q000276:immunology; D005260:Female; D018390:Gene Targeting; D018858:Germinal Center / Q000166:cytology / Q000276:immunology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010581:Peyer's Patches / Q000033:anatomy & histology / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D011947:Receptors, Antigen, B-Cell; D014763:Viral Matrix Proteins