Mice whose B cells cannot produce the T15 idiotype also lack an antigen-specific helper T cell required for T15 expression.

Abstract

The X-linked CBA/N defect in B cell function precludes an antibody response to phosphorylcholine (PC). Accordingly, (CBA/N X BALB/c)F1 male mice are unresponsive to PC and lack circulating immunoglobulin bearing the T15 idiotype characteristic of BALB/C anti-PC antibody. In contrast, (CBA/N X BALB/c)F1 female mice respond to PC and greater than 80% of the anti-PC antibody is T15+. No T-cell abnormalities are known to be associated with the CBA/N mutation. These experiments compared the ability of helper T cells from either (CBA/N X BALB/c)F1 male (T15-) or F1 female (T15+) mice to help F1 female B cells respond to PC and to influence the level of T15 expression. The results indicate that although F1 male T cells collaborated with F1 female B cells just as efficiently as F1 female T cells for the total anti-PC response, the percentage of T15 expression induced by F1 male T cells fell dramatically. The (CBA/N X BALB/c)F1 male thus appear to lack a helper T-cell subset required for dominant idiotype production. This helper T cell defect could be repaired by adding F1 female T cells primed to a second carrier to F1 male T cells and restimulating the cell mixture with PC coupled to the antigen used to prime the F1 male cells plus free second carrier. This result implies that conventional helper T cells derived from the F1 male donor can collaborate with a distinct helper T-cell subset from the F1 female donor which recognizes both carrier and idiotype to induce an anti-PC antibody response dominated by the T15 clonotype.

Antigen-specific helper T cells required for dominant production of an idiotype (THId) are not under immune response (Ir) gene control.

“…It has been previously established that the dominant production of T 15 idiotype in the antibody response to PC-proteins requires two distinct Th (11,12). One Th cell set is present in both carrier-primed normal mice and mice treated from birth with anti-/z antibody.…”

“…The preparation, purification, and testing of anti-T15 idiotype antibodies have been described previously (11,16). Hybridoma anti-Thy-l.2 was kindly provided by Dr. J. Sprent, Wistar Institute, Philadelphia, Pa.…”

“…The preparation of antigens used in these experiments has been described previously (11,16). The preparation of GLPhe utilized in these studies was prepared and analyzed as previously described (14).…”

“…This was carried out as previously described (11,16). Briefly, graded numbers of primed T and B cells, 25 #g of PC-KLH, and, as appropriate, 25 #g OVA or 50 gg GLPhe were injected intravenously into syngeneic irradiated recipients.…”

Role of variable region gene expression and environmental selection in determining the antiphosphorylcholine B cell repertoire.

“…The results presented in this report demonstrate that the extraordinarily high frequency of mature B cells of the T15 clonotype can be accounted for by an equally high frequency of B cells of this clonotype that emerge from the generative cell pool in the bone marrow. Thus, while these findings do not rule out idiotype-specific or antigen-specific selection as contributors to the high frequency of T15 B cells (31,32), they obviate the necessity of such explanations to account for the high frequency of this clonotype. It should be noted that recent investigations using polyclonal stimulation of splenic and immature bone marrow cell populations have led to similar conclusions concerning cells expressing the NP b idiotype in C57BL/6 mice (33) and the 460 idiotype in BALB/c mice (34).…”