FOLLICULAR DENDRITIC CELLS, INTERDIGITATING CELLS, AND CELLS OF THE MONOCYTE-MACROPHAGE LINEAGE ARE THE C1Q-PRODUCING SOURCES IN THE SPLEEN- IDENTIFICATION OF SPECIFIC CELL-TYPES BY IN-SITU HYBRIDIZATION AND IMMUNOHISTOCHEMICAL ANALYSIS

In a mouse model, we have shown previously that macrophages are the pr incipal source of complement C1q. Furthermore, spleen, heart, and brai n were found to contain substantial levels of murine C1q-specific mRNA , whereas liver, kidney, lung, and small intestine contained only trac e amounts of C1q-specific mRNA. This work addresses the identification of C1q-expressing spleen cells in the rat, using Northern blotting an d in situ detection of rat C1q mRNA combined with immunohistochemical analysis. The complete sequence of mRNA encoding the B chain of rat C1 q was established. The cloned cDNA was found to hybridize primarily wi th spleen-derived mRNA of 1.2 kb, and additionally with a novel mRNA s pecies of 3 kb. In situ hybridization together with immunohistochemist ry revealed most of the C1q-expressing cells to be located in the red pulp of the spleen, and to be mainly of the monocyte-macrophage lineag e, as indicated by coexpression of ED-1, an established marker for thi s type of cell. In addition, C1q was expressed in S-100-positive but E D-1-negative cells, in germinal center follicular dendritic cells, and in some interdigitating dendritic cells of the periarteriolar lymphat ic sheath (PALS). These results indicate that the spleen, containing t he above APCs that are all involved to a major extent in the adaptive immune response and are all capable of synthesizing C1q that is involv ed intimately in the innate immune response, may provide the site at w hich the innate and adaptive immune systems merge.