Relative contribution of T and B cells to hypermutation and selection of the antibody repertoire in germinal centers of aged mice.

The immune system of aged individuals often produces antibodies that have lower affinity and are less protective than antibodies from young individuals. Recent studies in mice suggested that antibodies produced by old individuals may be encoded by distinct immunoglobulin (Ig) genes and that the somatic hypermutation process in these individuals is compromised. The present study employed Ighb scid mice reconstituted with normal lymphocytes from young (2-3-mo-old) and aged (20-25-mo-old) donors and immunized with a protein conjugate of the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP) to determine whether the molecular changes in antibody repertoire reflect senescence in the B cells or whether they are mediated by the aging helper T lymphocytes.

Facultative role of germinal centers and T cells in the somatic diversification of IgVH genes.

The development of memory B cells takes place in germinal centers (GC) of lymphoid follicles where antigen-driven lymphocytes undergo somatic hypermutation and affinity selection, presumably under the influence of helper T cells. However, the mechanisms that drive this complex response are not well understood. We explored the relationship between GC formation and the onset of hypermutation in response to the hapten phosphorylcholine (PC) coupled to antigenic proteins in mice bearing different frequencies of CD4+ T cells.

Repertoire diversity of antibody response to bacterial antigens in aged mice. IV. Study of VH and VL gene utilization in splenic antibody foci by in situ hybridization.

Mouse Abs against a bacterial epitope, the phosphorylcholine (PC) hapten are encoded by the T15 genes VH1(S107) and V kappa 22. It has been shown that PC-specific hybridomas from aged animals often express IgV gene families other than T15. To determine the extent of this age-dependent molecular shift in the anti-PC response, we examined antibody-forming cells (AFC) in individual young (2 to 4 month) and aged (20 to 24 month) mice by an in situ RNA hybridization.

Distinct pathways of B cell differentiation. I. Residual T cells in athymic mice support the development of splenic germinal centers and B cell memory without an induction of antibody.

B cell memory to T cell-dependent Ags develops in the germinal centers (GC). Here we report that thymus-deficient, nu/nu mice immunized with phosphorylcholine coupled to keyhole limpet hemocyanin (EPC-KLH) develop GC in the spleen in the absence of Ab-forming cell (AFC) response. However, the formation of GC on EPC-KLH immunization requires T cells, because 1) CB.

Exogenous interleukin-2 abrogates differences in the proliferative responses to T cell mitogens among inbred strains of mice.

The proliferative response of spleen cells from BALB/c mice to stimulation with a T cell mitogen, concanavalin A (Con A), was two or more times stronger than that of cells from C57BL/10SnSc (B10) mice. In contrast, the cells from B10 mice responded better to B cell mitogen bacterial lipopolysaccharide (LPS). The differences in the proliferative response to Con A stimulation were not associated with the function of macrophages nor did they depend on IL-1.