Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine.

An Ig molecule containing L chains and H chains similar to human delta-chains has been detected on the surface of radioiodinated murine lymphoid cells. Newborn mice have only IgM on their splenocytes. Between 10 and 15 days, the IgD-like molecule appears and increases in amount until 3 mo of age, when it is the predominant cell surface Ig in terms of radioactivity. IgD is found only in peripheral lymphoid tissues and is present in larger amounts on peripheral lymph node cells (approximately 85% of surface Ig) than on splenocytes (approximately 50%). IgD is also present in comparable amounts on cells from both nu/nu and germfree mice, indicating that its expression may be independent of both thymic influence and antigenic stimulation. These studies suggest that there is a switch from cell surface IgM to IgD that occurs during differentiation of virgin B lymphocytes in the spleen.

Immune responsiveness of inbred mice to low doses of ovalbumin or ovomucoid is under control of single dominant genes closely linked to alleles of the H-2 locus. High responsiveness to ovomucoid is linked with the H-2a and H-2k alleles, and to ovalbumin with the H-2b, H-2d, and H-2q alleles.

The secretory immune system of the mammary gland is undeveloped in virgin mice but becomes active at term and during lactation. This change appears to depend on migration to the mammary gland of precursors of IgA-secreting cells derived from the gut-associated lymphoid tissue, an origin which explains the specificity of milk IgA antibodies for enteric organisms. Because development of the epithelial components of the mammary gland is clearly under hormonal control, we examined the effect of mammotro ic hormones on differentiation of the immune elements. Undr a combined regimen of progesterone, estrogen, and prolactin, development of the glandular epithelium occurs with concomitant increments in the number of IgA-secreting plasma cells and amount of intrae ithelial IgA. These increases appear to be due to en-

The fate of mesenteric lymph node lymphoblasts labeled with either [125I]iododeoxyuridine or [3H]thymidine can be studied after intravenous transfer into syngeneic mice both by measurement of radioactivity in various organs and by combined immunofluorescence and autoradiography of recipient tissues. Many of the lymphoblasts home to the lamina propria of the small intestine within hours of transfer; of these, many visibly secrete IgA. To determine whether the cells that will ultimately secrete IgA are already committed to IgA synthesis before their arrival in the gut, mesenteric lymph node cell populations were treated with various class-specific antisera to mouse immunoglobulins before transfer. Treatment with antiserum to IgA, plus complement, reduced the fraction of injected label recovered from the recipients' intestines, and also reduced the proportion of donor (labeled) cells containing IgA. We conclude that mesenteric lymph nodes are probably the principal source of IgA-secreting plasma cells in the lamina propria of the gut, and that the cells become committed to IgA synthesis and develop cell surface IgA before emigrating. This IgA is apparently synthesized by the cells that bear it since it is not removed by extensive rinsing at 37 degrees C, a maneuver that elutes passively adsorbed immunoglobulin.

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Antigen-antibody complexes bind to the surface of macrophages even when little or no binding of antibody alone can be demonstrated (1-5). Binding of complexes is known to be mediated by the Fc region of the antibody molecules (2), and is inhibited by -F c but not -F(ab')2 fragments (6).It has been postulated that complex formation might cause an allosteric change in the antibody molecule, analogous to that observed in electron micrographs by Feinstein and Rowe (7) and Valentine and Green (8) and inferred from physical data by others (9-12). This might result in exposure of a binding site for the macrophage surface, the implication being that combination of the -F a b portions of the antibody molecule with antigen produces a conformational change in the -F c region. An alternative hypothesis, considered here, is that "free" antibody molecules may already have a binding site for the macrophage surface, but that binding is weak. Formation of a complex containing more than one antibody molecule, and thus more than one potential site of attachment, increases the strength of binding. This paper reports our studies on this problem using monovalent, divalent, and polyvalent haptens and labeled purified antibody to the hapten. It was found that monovalent hapten and polyvalent hapten in antigen excess were unable to enhance the binding of antibody to macrophages, whereas polyvalent hapten and divalent hapten at equivalence could do so. Binding of complexes was inhibited by normal rabbit gamma globulin previously cleared of aggregated molecules. Bound complex was eluted from macrophages less easily than was bound antibody alone. These results support the hypothesis that the enhancement of antibody binding to macrophages in the presence of antigen is due to increased energy of binding resulting from summation of individual binding sites, rather than to the occurrence of allosteric change. In addition, saturation studies using ultracentrifuged normal *

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