Lack of age‐associated auto‐anti‐idiotypic antibody regulation in mucosal‐associated lymph nodes

Abstract

It has previously been shown that the loss of immune competence in the splenic B cell population with age may be due to auto‐anti‐idiotypic antibody regulation (M. R. Szewczuk and R. J. Campbell, Nature 1980. 286: 164). In the present study we have investigated the appearance of auto‐anti‐idiotypic antibody on immune B cells from the mucosal‐associated lymph nodes of old and young mice of the same strain. Various aged C57BL/6J male mice were immunized with 500 μg trinitrophenylated bovine gamma globulin (TNP‐BGG) in complete Freund's adjuvant (CFA) intraperitoneally. IgM, IgG and IgA anti‐TNP plaque‐forming cell (PFC) responses in the spleen, mediastinal and mesenteric lymph nodes were assayed for anti‐idiotype‐blocked, hapten‐augmentable PFC, 14 days later. It was found that 8 months or older C57BL/6J male mice produced a significantly high percentage of hapten‐augmentable IgM, IgG and IgA anti‐TNP PFC in the spleen. In contrast, there was a lack of hapten‐augmentable anti‐TNP PFC in the mesenteric and mediastinal lymph nodes with increasing age of the animal. Mice receiving antigen in the footpads and base of the tail also produced a significantly high percentage of hapten‐augmentable IgG PFC in the draining peripheral lymph nodes. TNP‐ε‐amino‐n‐caproic acid (EACA) as hapten was shown to specifically augment anti‐TNP PFC. Immune sera from 15‐month‐old mice caused a specific inhibition of anti‐TNP PFC in vitro. The inhibition of plaque formation was completely reversible by addition of TNP‐EACA as hapten. This PFC inhibitory activity in immune sera lacked anti‐TNP antibody activity, but reacted with anti‐TNP antibody of C57BL/6J origin. Immune sera from 8 month or older mice also revealed anti‐(anti‐TNP F(ab')2 IgG) titer as assayed by passive hemagglutination. Thus, the results of this study indicate a division of the immune system into regulatory compartments. Auto‐anti‐idiotypic antibody may be involved in a down‐regulation of systemic responses but with no apparent effect in the mucosal‐associated lymph nodes.

Cross-Protective Immunity of Mice Induced by Oral Immunization with Pneumococcal Surface Adhesin A Encapsulated in Microspheres

“…Moreover, mucosal immunization could be a better alternative for young children and for the elderly, since the mucosal immune system develops earlier in infants and lasts longer in the elderly compared with the systemic immune system (16,37,44). Mucosal immunization is also beneficial for human immunodeficiency virus patients (41), because human immunodeficiency virus-infected subjects can develop normal mucosal antibody responses even in late clinical phases (15,22,29,33).…”

Age-Related Strain Differences in the Development of Auto-Anti-Idiotypic Antibody Regulation in the Splenic and Mucosal-Associated Lymphoid Systems

“…This heterogeneity re striction was not found in the mucosal tissues of the same mice [30]. (b) The magnitude of the anti-TNP PFC response in the mucosalassociated lymph nodes of old mice remains immunologically vigorous and unimpaired as compared with responses of young mice [31], In contrast, there was a reduction in the anti-TNP PFC response of the spleen and peripheral lymph nodes of old mice, (c) The appearance ofanti-idiotypc-blocked. haptenaugmentable PFC in the spleen and periph eral lymph nodes of aged mice following a primary immune response to TNP-BGG was not demonstrated in the MLN or BLN of these animals [29], Recently we have shown that strains of mice differ with regard to the age at which they produce anti-idiotype-blocked.…”

“…12, 29] which specifically inhibit idiotype-(anti-TNP antibody-)producing B cells in vitro [29]. These antibodies could bind anti-TNP antibodies of the same strain origin, but not TNP itself [29].…”

“…12, 29] which specifically inhibit idiotype-(anti-TNP antibody-)producing B cells in vitro [29]. These antibodies could bind anti-TNP antibodies of the same strain origin, but not TNP itself [29]. Furthermore, these anti bodies were of the IgG2a and lgG3 classes [27], and revealed anti-[anti-TNP F(ab'h IgG] titer as assayed by passive hemaggluti nation [27,29], In recent studies, it has been shown that auto-anti-idiotypic antibodies may be in part responsible for an age-associated decline in immune responsiveness to T-dependent [26,28] and T-independent [12,26] antigens.…”

“…This suppressive effect of auto-anti-idiotypic antibody was at tributed possibly to its simultaneous binding of surface Ig and Fc receptors on the surface of the B cell, thus inhibiting antibody secre tion [11], In previous studies, we have shown that the decline in the number of plaque forming cells (PFC), loss of high affinity PFC, and the increase in hapten-augmentable PFC with age in the spleen of C57BL/6J male mice may be due to auto-anti-idiotypic anti body regulation [28], In contrast, mucosal immunity in old C57BL/6J mice, as mea sured in PFC responses of the mediastinal (BLN) and mesenteric (MLN) lymph nodes, was not reduced [31]; further, there was no loss of high affinity antibody-secreting cells [30], and there was no appreciable appear ance of anti-idiotype-blocked, hapten-aug mentable PFC [29] in these areas. These find ings support the hypothesis that the systemic and mucosal B cell repertoires do not un dergo parallel changes with age [33].…”