Induction of B-cell development in adult mice reveals the ability of bone marrow to produce B-1a cells (original) (raw)

B cell repertoire in adult antigen-free and conventional neonatal balb/c mice

European Journal of Immunology, 1989

Early in ontogeny B cells preferentially use VH gene families which are most adjacent to the genes coding for the constant part of the immunoglobulin molecule. In conventional adult mice, however, a random usage of VH gene families has been found. We investigated the role of exogenous antigenic stimulation on this normalization of VH gene usage by B cells. Therefore, we made use of adult germ-free BALB/c mice fed a chemically defined ultrafiltered antigen-free diet (GF-CD) and neonatal conventional BALB/c mice. Both the adult GF-CD and the newborn conventional mice represent situations with minimal exogenous antigenic stimulation. The results obtained with RNA dot blot hybridization with probes specific for the different VH gene families showed in hybridomas from adult GF-CD BALB/c mice a preferential usage of the CH-proximal VH gene family PC7183. In hybridomas from 5-day-old conventional BALB/c mice a less frequent usage of the 5558 VH gene family was found and an increased usage of the PC7183 VH gene family than what would be expected from random usage. Evidence is presented that the RNA giving a positive signal with the PC7183 probe represents functional messages for IgM production.

Homeostasis of Peripheral B Cells in the Absence of B Cell Influx from the Bone Marrow

Journal of Experimental Medicine, 2001

To study homeostasis of peripheral B lymphocytes in the absence of B cell influx from the bone marrow, we generated a mouse mutant in which the recombination-activating gene ( RAG)-2 can be inducibly deleted. When RAG-2 was deleted at the age of 8-10 wk, splenic naive follicular B cells were gradually lost over a year of observation, with a half-life of ‫ف‬ 4.5 mo. By contrast, the pool of marginal zone B cells in the spleen and of B-1 cells in the peritoneal cavity were kept at normal level. In lymph nodes, ‫ف‬ 90% of the B cells were lost within 4 mo, and B cell numbers remained constant thereafter. Mice in which RAG-2 was deleted at birth maintained a small population of activated B cells with an increased proportion of marginal zone B cells. Additionally, an increase of the pool of IgM secreting cells and B-1a cells was observed.

Early and late B-cell development in the mouse

Current Biology, 1992

A common principle in B-cell development is the stringent selection of cells expressing appropriate antibody V regions as surface receptors. Cells failing to do so appear destined to rapid death. These lifedeath decisions are mediated by signals whose nature is not yet understood but whose generation involves immunoglobulin receptor complexes on B cells and B-cell progenitors.

B Cell Development in the Spleen Takes Place in Discrete Steps and Is Determined by the Quality of B Cell Receptor-derived Signals

2010

Only mature B lymphocytes can enter the lymphoid follicles of spleen and lymph nodes and thus efficiently participate in the immune response. Mature, long-lived B lymphocytes derive from short-lived precursors generated in the bone marrow. We show that selection into the mature pool is an active process and takes place in the spleen. Two populations of splenic B cells were identified as precursors for mature B cells. Transitional B cells of type 1 (T1) are recent immigrants from the bone marrow. They develop into the transitional B cells of type 2 (T2), which are cycling and found exclusively in the primary follicles of the spleen. Mature B cells can be generated from T1 or T2 B cells.

Human B cell growth and differentiation in the spleen of immunodeficient mice

The Journal of Immunology

Human mAbs (HumAbs) have therapeutic potential against infectious diseases and cancer. Heretofore, their production has been hampered by ethical constraints preventing the isolation of Ag-specific activated B cells by in vivo immunization. Alternatively, severe combined immune deficient (SCID) mice, transplanted i.p. with human (Hu)-PBLs, allow the in vivo stimulation of human Ab responses without the usual constraints. Unfortunately, human B cells only represent a minor fraction of the surviving graft, they are scattered all over the animal body, and thus are hard to isolate for subsequent immortalization procedures. To prevent this dispersion and to provide the human B cells with a niche for expansion and maturation, SCID mice were engrafted with Hu-PBL directly into the spleen. Simultaneously endogenous murine NK cell activity was depleted by treatment with an anti-mouse IL-2 receptor beta-chain Ab. During engraftment, human B lymphocytes became activated, divided intensely, and ...