Production of auto-antiidiotypic antibody during the normal immune response. VII. Analysis of the cellular basis for the increased auto-antiidiotype antibody production by aged mice.

Abstract

We have previously shown that old mice produce more hapten-augmentable plaque-forming cells (PFC) than do young animals, suggesting a greater auto-antiidiotype antibody (auto anti-Id) component in their immune response. In the present studies this is confirmed serologically. The marked auto-anti-Id response of aged mice can be transferred to lethally irradiated young recipients with spleen but not bone marrow cells from old donors, suggesting that it is an intrinsic property of their peripheral B cell population and that the distribution of Id arising from the bone marrow of old and young mice is similar. In contrast with young mice the auto-anti-Id response of old animals is relatively T cell-independent and old donors do not show an increase in their ability to transfer an auto-anti-Id response after priming with TNP-F. These observations suggest that old mice behave as if already primed for auto-anti-Id production. Irradiated mice reconstituted with bone marrow cells from either young or old donors together with splenic T cells from old donors generate a relatively large auto-anti-Id response, whereas mice reconstituted with bone marrow from either young or old donors together with splenic T cells from young donors produce few hapten-augmentable PFC. It is suggested that differences in Id expression and auto-anti-Id production are the consequences of the interaction of Id (and anti-Id) arising from the marrow with anti-Id (and Id) present in the peripheral T cell population which serves as a repository of information about shifts in Id distribution, resulting from lifelong interactions with environmental and self-antigens.

Immunoresponses to Neisseria meningitidis epitopes: in vivo analysis of immunocompetent cells involved in suppression of secondary response to phosphorylcholine

“…The augmentable PFCs, which are responsible for the overshooting, have in most cases been shown to be terminally differentiated B cells which are blocked by auto-anti-idiotypic (auto-antiid) antibodies attached to their surface [9,20,48]. Evidence exists that auto-antiid B cells are under T helper (Th) control [2,21,24,28,49,53], and therefore it dan reasonably be hypothesized that priming hosts with NMB triggers a mechanism that activates Ta cells specific for those B cells which produce anti-id antibodies. These B cells, according to the network theory [27], are internal images of the antigen and bind anti-PC antibodies.…”

Aging and the Immune Response

“…Goidl and colleagues (Goidl, et al, 1983;Goidl, Thorbecke, Weksler, & Siskind, 1980;McEvoy & Goidl, 1988) have at tributed an age-dependent loss in high-af finity antibody-secreting cells to a T-celldependent production of anti-idiotypic antibody ("anti-Id" antibody, i.e., anti body that is itself specific for particular immunoglobulin determinants) that they find can inhibit secretion of the high-af finity Ig. Szewczuk and Campbell (1980) have also found evidence for a strong influ ence of anti-Id antibodies on B-cell respon siveness in old mice.…”

Bone marrow function. I. Peripheral T cells are responsible for the increased auto-antiidiotype response of older mice.

“…TNP PFC in individual mouse spleens or individual culture dishes were assayed by a slide modification of the Jerne plaque technique using 2,4,6-trinitrophenylated sheep red blood cells (TNP-SRBC) as described (1,2). Also, anti-TNP PFC assays were performed with concentrations of TNP-EACA (epsilon aminocaproic acid) in the agar ranging from 1 × 10 -9 tO 1 × 10 -~ in half-log units.…”