CD19 function in early and late B cell development. II. CD19 facilitates the pro-B/pre-B transition.
Proliferative expansion of pro-B cells is an IL-7-dependent process that allows for the rearrangement of H chain genes and the expression of the pre-B cell receptor (pre-BCR). Further B cell differentiation is dependent upon signals elicited through the pre-BCR, which are thought to be responsible for allelic exclusion, induced L chain gene rearrangement, and continued proliferation. CD19 promotes the proliferation and survival of mature B cells, but its role in early B cell development is less well understood. Here we identify and characterize impairments in early B cell development in CD19(-/-) mice. Following sublethal irradiation, we found decreased numbers of autoreconstituted early B cells, which was first evident in the large cycling pre-B cell fraction. Reduced cell progression due to a defect in proliferation was made evident from cell cycle analysis and bromodeoxyuridine labeling of bone marrow cells from CD19(-/-) and wild-type mice. Studies of IL-7-dependent pre-B cell cultures derived from wild-type and CD19(-/-) mouse bone marrow suggested that CD19 has little affect on IL-7 signaling. By contrast, signaling through the pre-BCR was impaired in the absence of CD19, as demonstrated by reduced activation of Bruton's tyrosine kinase and extracellular signal-regulated kinase/mitogen-activated protein kinase. Thus, in addition to promoting mature B cell homeostasis and Ag-induced responses, the early onset of CD19 expression acts to enhance B cell generation.
Otero
Dennis C
DC
Division of Biology and University of California-San Diego Cancer Center, La Jolla, CA 92093, USA.
Rickert
Robert C
RC
D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000502:physiology*; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000528:radiation effects; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D003433:Crosses, Genetic; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054420:Pre-B Cell Receptors; D011828:Radiation Chimera / Q000276:immunology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis* / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology
D018941:Antigens, CD19; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell